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Sample records for c-peptide

  1. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  2. Intracellular signalling by C-peptide.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2008-01-01

    C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na(+)/K(+) ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes. PMID:18382618

  3. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  4. C-Peptide and its intracellular signaling.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2009-01-01

    Although long believed to be inert, C-peptide has now been shown to have definite biological effects both in vitro and in vivo in diabetic animals and in patients with type 1 diabetes. These effects point to a protective action of C-peptide against the development of diabetic microvascular complications. Underpinning these observations is undisputed evidence of C-peptide binding to a variety of cell types at physiologically relevant concentrations, and the downstream stimulation of multiple cell signaling pathways and gene transcription via the activation of numerous transcription factors. These pathways affect such fundamental cellular processes as re-absorptive and/or secretory phenotype, migration, growth, and survival. Whilst the receptor remains to be identified, experimental data points strongly to the existence of a specific G-protein-coupled receptor for C-peptide. Of the cell types studied so far, kidney tubular cells express the highest number of C-peptide binding sites. Accordingly, C-peptide exerts major effects on the function of these cells, and in the context of diabetic nephropathy appears to antagonise the pathophysiological effects of major disease mediators such as TGFbeta1 and TNFalpha. Therefore, based on its cellular activity profile C-peptide appears well positioned for development as a therapeutic tool to treat microvascular complications in type 1 diabetes. PMID:20039003

  5. Human C-peptide. Pt. 1

    International Nuclear Information System (INIS)

    Synthetic human C-peptide bearing a tyrosine group at its amino end is labelled with 125iodine using chloramin T or hydrogen peroxide and lactoperoxidase. The results of the two methods are compared. Antiserum to synthetic human C-peptide (without tyrosine), which was partially coupled to rabbit albumin, is raised in guinea pigs and goats. Goats show to be superior to guinea pips concerning antibody production. The so-called 'hook effect' phenomenon is observed when setting up the standard curves for the radioimmunoassay. Monotonically decreasing standard curves are obtained on dilution of antiserum with a high antibody titer which was produced by repeated immunization in goats. Free C-peptide and C-peptide bound to antiserum are separated using the anion exchange resin amberlite. Using this separation technique we excluded unspecific binding of labelled C-peptide to protein fractions in serum of diabetics. The sensitivity of our radioimmunoassay is approx. 0.3 ng C-peptide/ml serum. Intra- and interassay variability are below 10%. Human proinsulin is the only substance found to crossreact with the antiserum. (orig.)

  6. Radioimmunoassay for C-peptide and proinsulin

    International Nuclear Information System (INIS)

    Proinsulin, the biosynthetic precursor of insulin, was discovered by Steiner et al. (1967) and shown to be converted to insulin and C-peptide in the β-cell. The first part of this paper deals with aspects of the radioimmunoassay for C-peptide with special emphasis on the development and the sources of errors encountered in our laboratory (Heding, 1975; Naithani et al., 1975). The second part deals with the many problems involved in the determination of human proinsulin and describes a direct and specific radioimmunoassay developed for measuring proinsulin in serum with a detection limit of less than 0.01 pmol/ml. (Auth.)

  7. C-peptide and Diabetic Encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun Cai; Hui-qin Xu; Yi Lu

    2011-01-01

    With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive fimctions.Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system,hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide defidency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients.Those Findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

  8. Fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and urinary C-peptide in relation to clinical type of diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated...... with a fasting plasma C-peptide value less than 0.20 nmol/l, a glucagon stimulated plasma C-peptide value less than 0.32 nmol/l, and a urinary C-peptide value less than 3.1 nmol/l, or less than 0.54 nmol/mmol creatinine/24 h, or less than 5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C...

  9. Immunological half-life of porcine proinsulin C-peptide

    International Nuclear Information System (INIS)

    Immunological half-lifes of injected porcine C-peptide and insulin with RIA were studied and calculated as 9.8 and 8.0 minutes. Higher circulating levels of C-peptide as compared to insulin in normal young swines lead to speculation about a longer half-life of C-peptide. This hypothesis was verified in this study. Immunological half-lifes of porcine proinsulin and insulin in the pig were 20 and 6 minutes, respectively. (GSE)

  10. History and diagnostic significance of C-peptide.

    Science.gov (United States)

    Brandenburg, Dietrich

    2008-01-01

    Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rapidly growing number of clinical investigations. A prerequisite was the development of specific immuno assays for proinsulin and C-peptide. Further milestones were: the chemical synthesis of several C-peptides and the accomplishments in the synthesis of proinsulin; the detection of preproinsulin with its bearings on understanding protein biosynthesis; the pioneering role of insulin, proinsulin, C-peptide, and mini-C-peptides in the development of recombinant DNA technology; and the discovery of the enzymes for the endoproteolytic processing of proinsulin into insulin and C-peptide, completing the pathway of biosynthesis. Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions. PMID:18509495

  11. C-Peptide Effects on Renal Physiology and Diabetes

    Directory of Open Access Journals (Sweden)

    L. Rebsomen

    2008-01-01

    Full Text Available The C-peptide of proinsulin is important for the biosynthesis of insulin and has for a long time been considered to be biologically inert. Animal studies have shown that some of the renal effects of the C-peptide may in part be explained by its ability to stimulate the Na,K-ATPase activity. Precisely, the C-peptide reduces diabetes-induced glomerular hyperfiltration both in animals and humans, therefore, resulting in regression of fibrosis. The tubular function is also concerned as diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with the reduction of the diabetes-induced glomerular hyperfiltration. The tubular effectors of C-peptide were considered to be tubule transporters, but recent studies have shown that biochemical pathways involving cellular kinases and inflammatory pathways may also be important. The matter theory concerning the C-peptide effects is a metabolic one involving the effects of the C-peptide on lipidic metabolic status.This review concentrates on the most convincing data which indicate that the C-peptide is a biologically active hormone for renal physiology.

  12. Proinflammatory Effects of C-Peptide in Different Tissues

    Directory of Open Access Journals (Sweden)

    Dusica Vasic

    2012-01-01

    Full Text Available Atherosclerosis is well known as an inflammatory disease that can lead to clinical complications such as heart attack or stroke. C-peptide as a cleavage product of proinsulin is in the last few decades known as an active peptide with a number of different effects on microvascular and macrovascular complications in type 2 diabetic patients. Patients with insulin resistance and early type 2 diabetes show elevated levels of C-peptide in blood. Several last findings demonstrated deposition of C-peptide in the vessel wall in ApoE-deficient mice and induction of local inflammation. Besides that, C-peptide has proliferative effects on human mesangial cells. This review discusses recently published proinflammatory effects of C-peptide in different tissues.

  13. Proinsulin C-peptide interferes with insulin fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  14. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  15. Cellular and physiological effects of C-peptide.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2009-04-01

    In recent years, accumulating evidence indicates a biological function for proinsulin C-peptide. These results challenge the traditional view that C-peptide is essentially inert and only useful as a surrogate marker of insulin release. Accordingly, it is now clear that C-peptide binds with high affinity to cell membranes, probably to a pertussis-toxin-sensitive G-protein-coupled receptor. Subsequently, multiple signalling pathways are potently and dose-dependently activated in multiple cell types by C-peptide with the resulting activation of gene transcription and altered cell phenotype. In diabetic animals and Type 1 diabetic patients, short-term studies indicate that C-peptide also enhances glucose disposal and metabolic control. Furthermore, results derived from animal models and clinical studies in Type 1 diabetic patients suggest a salutary effect of C-peptide in the prevention and amelioration of diabetic nephropathy and neuropathy. Therefore a picture of Type 1 diabetes as a dual-hormone-deficiency disease is developing, suggesting that the replacement of C-peptide alongside insulin should be considered in its management. PMID:19243312

  16. History and Diagnostic Significance of C-Peptide

    OpenAIRE

    Dietrich Brandenburg

    2008-01-01

    Starting with the epoch-making discovery of proinsulin, C-peptide has played an important interdisciplinary role, both as part of the single-chain precursor molecule and as an individual entity. In the pioneering years, fundamental systematic experiments unravelled new biochemical mechanisms and chemical structures. After the first detection of C-peptide in human serum, it quickly became a most useful independent indicator of insulin biosynthesis and secretion, finding application in a rap...

  17. C-Peptide: A New Mediator of Atherosclerosis in Diabetes

    Directory of Open Access Journals (Sweden)

    Dusica Vasic

    2012-01-01

    Full Text Available Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients.

  18.  Pleiotropic action of proinsulin C-peptid

    Directory of Open Access Journals (Sweden)

    Michał Usarek

    2012-03-01

    Full Text Available  Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na /K -ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

  19. C peptides as entry inhibitors for gene therapy.

    Science.gov (United States)

    Egerer, Lisa; Kiem, Hans-Peter; von Laer, Dorothee

    2015-01-01

    Peptides derived from the C-terminal heptad repeat 2 region of the HIV-1 gp41 envelope glycoprotein, so-called C peptides, are very potent HIV-1 fusion inhibitors. Antiviral genes encoding either membrane-anchored (ma) or secreted (iSAVE) C peptides have been engineered and allow direct in vivo production of the therapeutic peptides by genetically modified host cells. Membrane-anchored C peptides expressed in the HIV-1 target cells by T-cell or hematopoietic stem cell gene therapy efficiently prevent virus entry into the modified cells. Such gene-protection confers a selective survival advantage and allows accumulation of the genetically modified cells. Membrane-anchored C peptides have been successfully tested in a nonhuman primate model of AIDS and were found to be safe in a phase I clinical trial in AIDS patients transplanted with autologous gene-modified T-cells. Secreted C peptides have the crucial advantage of not only protecting genetically modified cells from HIV-1 infection, but also neighboring cells, thus suppressing virus replication even if only a small fraction of cells is genetically modified. Accordingly, various cell types can be considered as potential in vivo producer cells for iSAVE-based gene therapeutics, which could even be modified by direct in vivo gene delivery in future. In conclusion, C peptide gene therapeutics may provide a strong benefit to AIDS patients and could present an effective alternative to current antiretroviral drug regimens. PMID:25757622

  20. Radioimmunoassay for C-peptide in diabetic children

    International Nuclear Information System (INIS)

    Direct insulin radioimmunoassay (RIA) studies in a diabetic are no longer meaningful once insulin therapy has been instituted. For this reason, use is made of RIA for blood C-peptide, a proinsulin component reflecting endogenous insulin secretion independently of insulin therapy. The paper reports experience with C-peptide RIA studies carried out on blood from 273 diabetic children of normal body weight and 11.3 years average age, as well as 31 healthy children (control group). Diabetes duration ranged from 7 days to 14 years. The basic level of C-peptide in diabetic children is lower than that of healthy ones. Glucose stimulation produces C-peptide elevation in healthy but not in diabetic children. Glucagon stimulation produced a further rise of blood C-peptide in the healthy children. Diabetics showed very modest response to glucagon stimulation. C-peptide secretion in diabetic children proved to be inversely proportional to the duration of the diabetes. These findings in children with diabetes mellitus indicated their insulin secretion by beta cells of the pancreatic islets of Langerhans to be substantially decreased and unresponsive to glucose and glucagon stimulation. 3 figs, 1 tab

  1. Studies on human proinsulin.C-peptide radioimmunoassay method

    International Nuclear Information System (INIS)

    125I-labelled human.C-peptide was prepared by the chloramin T method, the enzymic method and the active ester method, respectively. Using respective 125I-labelled human.C-peptides in human proinsulin.C-peptide RIA, we compared the binding (B0/T %) to antibody, displacement by standard human.C-peptide, recovery, and stability. The usable 125I-labelled antigen for human proinsulin.C-peptide RIA could be prepared by the chloramin T method and the enzymic method which labelled 125I to tyrosyl human proinsulin connecting peptide, and by an active ester method which conjugates 125I-labelled active ester to human proinsulin connecting peptide. No differences among those 125I-labelled antigens were observed in displacement (B/B0 %) by standard human.C-peptide or the recovery test. In the case of constant preparation of 125I-labelled antigen for RIA, the enzymic method was the best from the viewpoint that reaction ratio is stable and the stability of B0/T % was good. (auth.)

  2. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    International Nuclear Information System (INIS)

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  3. History and Diagnostic Significance of C-Peptide

    Directory of Open Access Journals (Sweden)

    Dietrich Brandenburg

    2008-01-01

    Today, C-peptide continues to serve as a special diagnostic tool in Diabetology and related fields. Thus, its passive role is well established. Evidence for its active role in physiology and pathophysiology is more recent and is subject of the following contributions.

  4. Correlations between fasting plasma C-peptide, glucagon-stimulated plasma C-peptide, and urinary C-peptide in insulin-treated diabetics

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Frøland, A;

    1987-01-01

    This study correlated fasting plasma C-peptide (CP), plasma CP 6 min after stimulation with 1 mg glucagon i.v., and the mean of three 24-h urinary excretions of C-peptide (UCP)/creatinine in 132 insulin-treated diabetics. Patients were divided into three groups: group 1, stimulated CP less than 0.......06 nM (n = 51); group 2, stimulated CP 0.06-0.60 nM (n = 48); and group 3, stimulated CP greater than 0.60 nM (n = 33). In all patients fasting CP was closely correlated to stimulated CP (r = .988, P less than .001), whereas the correlations between UCP and both fasting CP (r = .904, P less than .001......) and stimulated CP r = .902, P less than .001) were slightly less pronounced. The associations between UCP and both fasting CP (r = .716, P less than .001) and stimulated CP (r = .731, P less than .001) were modest in group 2, and even more so in group 3 (r = .557, P less than .001 and r = .641, P less than .001...

  5. Measurement of plasma canine C peptide by radioimmunoassay

    International Nuclear Information System (INIS)

    A sensitive radioimmunoassay for canine C peptide (CCP) was established using synthetic CCP, a specific antiserum, and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations have been used for 6 weeks after iodination. The standard curve ranges from 0.028 to 3.0 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.3 and 0.8 nmol/l. The average recovery of CCP added to plasma samples was 100.6% (n = 9). Canine insulin, porcine proinsulin, bovine proinsulin, and human C peptide exhibited no cross-reactivity. The mean fasting plasma CCP concentration was 0.089 +- 0.021 nmol/l in normal dogs and -0.005 +- 0.007 nmol/l (mean +- SEM) in diabetic dogs, respectively. (author)

  6. Preparation of Tyr-C-peptide from genetically altered human insulin presursor

    Energy Technology Data Exchange (ETDEWEB)

    Huaiyu Sun; Jianguo Tang; Meihao Hu [Peking Univ., Beijing (China)

    1995-12-01

    C-peptide radiommunoassay (C-peptide RIA) is widely used in determination of pancreatic B-cell secretion activity. {sup 125}I labeled Tyr-C-peptide is indispensable in C-peptide RIA kit. Herein we discuss a way of obtaining recombinant Tyr-C-peptide. Arg32Tyr human proinsulin mutant (R32Y-proinsulin) gene was constructed by site-directed mutagenesis and overexpressed in Escherichia coli. Purified R32Y-proinsulin was converted to insulin and Tyr-C-peptide by trypsin and carboxypeptidase B codigestion. Tyr-C-peptide was isolated through reverse-phase HPLC (RP-HPLC) and identified by C-peptide RIA and amino acid analysis. 12 refs., 5 figs., 1 tab.

  7. C-Peptide and Atherogenesis: C-Peptide as a Mediator of Lesion Development in Patients with Type 2 Diabetes Mellitus?

    Directory of Open Access Journals (Sweden)

    Nikolaus Marx

    2008-01-01

    Full Text Available Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential role of C-peptide in atherogenesis in patients with type 2 diabetes.

  8. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans;

    1990-01-01

    not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...... for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we...

  9. Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

    OpenAIRE

    Shafqat, J.; Melles, E.; Sigmundsson, K.; Johansson, B.-L.; Ekberg, K; Alvelius, G.; Henriksson, M; Johansson, J; Wahren, J; Jörnvall, H

    2006-01-01

    Abstract. Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. I...

  10. C-peptide promotes lesion development in a mouse model of arteriosclerosis.

    Science.gov (United States)

    Vasic, Dusica; Marx, Nikolaus; Sukhova, Galina; Bach, Helga; Durst, Renate; Grüb, Miriam; Hausauer, Angelina; Hombach, Vinzenz; Rottbauer, Wolfgang; Walcher, Daniel

    2012-04-01

    Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show elevated serum levels of the proinsulin cleavage product C-peptide and immunohistochemical data from our group revealed C-peptide deposition in early lesions of these individuals. Moreover, in vitro studies suggest that C-peptide could promote atherogenesis. This study examined whether C-peptide promotes vascular inflammation and lesion development in a mouse model of arteriosclerosis. ApoE-deficient mice on a high fat diet were treated with C-peptide or control injections for 12 weeks and the effect on lesion size and plaque composition was analysed. C-peptide treatment significantly increased C-peptide blood levels by 4.8-fold without having an effect on glucose or insulin levels, nor on the lipid profile. In these mice, C-peptide deposition in atherosclerotic plaques was significantly increased compared with controls. Moreover, lesions of C-peptide-treated mice contained significantly more macrophages (1.6 ± 0.3% versus 0.7 ± 0.2% positive area; P arteriosclerosis support the hypothesis that C-peptide may have an active role in atherogenesis in patients with diabetes and insulin resistance.

  11. Application of reaction type of C-peptide release test in diabetes mellitus

    International Nuclear Information System (INIS)

    The author is to confirm the effect of C-peptide release test and types of release reaction in appraisal of pancreas function of β-cell and selection of treatment for diabetes mellitus (DM) patients. The serum C-peptide release test of 67 normal controls and 217 DM patients were determined by RIA, and the results were analyzed and compared. C-peptide release test can reflect the pancreas function of β-cell better, the peak of C-peptide ≥ 0.6 nmol/L after lunch can be the limit of whether to reduce the level of blood glucose only by oral drug. The authors should adjust the treatment through analyzing the type of C-peptide release reaction. C-peptide release test is very important in evaluating the pancreas function of β-cell, classifying the type of DM and selecting the treatment

  12. Urinary C-Peptide Tracks Seasonal and Individual Variation in Energy Balance in Wild Chimpanzees

    OpenAIRE

    Wrangham, Richard W.; Thompson, Melissa Emery; Muller, Martin N; Lwanga, Jeremiah S; Potts, Kevin B.

    2009-01-01

    C-peptide of insulin presents a promising new tool for behavioral ecologists that allows for regular, noninvasive assessment of energetic condition in wild animals. C-peptide is produced on an equimolar basis with insulin, thus is indicative of the body's response to available glucose and, with repeated measurement, provides a biomarker of energy balance. As yet, few studies have validated the efficacy of C-peptide for monitoring energy balance in wild animals. Here, we assess seasonal and in...

  13. C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis

    OpenAIRE

    Shaw, James A.; Partha Shetty; Burns, Kevin D.; Dean Fergusson; Greg A Knoll

    2015-01-01

    C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animal...

  14. Urinary C-peptide tracks seasonal and individual variation in energy balance in wild chimpanzees.

    Science.gov (United States)

    Emery Thompson, Melissa; Muller, Martin N; Wrangham, Richard W; Lwanga, Jeremiah S; Potts, Kevin B

    2009-02-01

    C-peptide of insulin presents a promising new tool for behavioral ecologists that allows for regular, non-invasive assessment of energetic condition in wild animals. C-peptide is produced on an equimolar basis with insulin, thus is indicative of the body's response to available glucose and, with repeated measurement, provides a biomarker of energy balance. As yet, few studies have validated the efficacy of C-peptide for monitoring energy balance in wild animals. Here, we assess seasonal and interindividual variation in urinary C-peptide concentrations of East African chimpanzees (Pan troglodytes schweinfurthii). We assayed 519 urine samples from 13 adult male chimpanzees in the Kanyawara community of Kibale National Park, Uganda. C-peptide levels were significantly predicted by the total amount of fruit and the amount of preferred fruit in the diet. However, chimpanzees had very low C-peptide titers during an epidemic of severe respiratory illness, despite highly favorable feeding conditions. Kanyawara males had significantly lower C-peptide levels than males at Ngogo, a nearby chimpanzee community occupying a more productive habitat. Among Kanyawara males, low-ranking males had consistently higher C-peptide levels than dominant males. While counterintuitive, this result supports previous findings of costs associated with dominance in male chimpanzees. Our preliminary investigations demonstrate that C-peptide has wide applications in field research, providing an accessible tool for evaluating seasonal and individual variation in energetic condition, as well as the costs of processes such as immune function and reproduction. PMID:19084530

  15. Human Proinsulin C-peptide from a Precursor Overexpressed in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    Yang-Bin HUANG; Jun REN; You-Shang ZHANG; Jiang LI; Xin GAO; Jiu-Ru SUN; Yi LU; Tao FENG; Jian FEI; Da-Fu CUI; Qi-Chang XIA

    2006-01-01

    In this article we report the production of human proinsulin C-peptide with 31 amino acid residues from a precursor overexpressed in Pichia pastoris. A C-peptide precursor expression plasmid containing nine C-peptide genes in tandem was constructed and used to transform P. pastoris. Transformants with a high copy number of the C-peptide precursor gene integrated into the chromosome of P. pastoris were selected. In high-density fermentation in a 300 liter fermentor using a simple culture medium composed mainly of salt and methanol, the C-peptide precursor was overexpressed to a level of 2.28 g per liter. A simple procedure was established to purify the expression product from the culture medium. The purified C-peptide precursor was converted into C-peptide by trypsin and carboxypeptidase B joint digestion. The yield of C-peptide with a purity of 96% was 730 mg per liter of culture. The purified C-peptide was characterized by mass spectrometry, N- and C-terminal amino acid sequencing, and sodium dodecylsulfate-polyacrylamide gel electrophoresis.

  16. Proinsulin C-peptide: Friend or foe in the development of diabetes-associated complications?

    Directory of Open Access Journals (Sweden)

    Lina Nordquist

    2008-09-01

    Full Text Available Lina Nordquist1, M Johansson21Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden; 2Department of Pathology, University of California, San Francisco, San Francisco, USAAbstract: The proinsulin connecting peptide, C-peptide, is a cleavage product of insulin synthesis that is co-secreted with insulin by pancreatic β-cells following glucose stimulation. Recombinant insulin, used in the treatment of diabetes, lacks C-peptide and preclinical and clinical studies suggest that lack of C-peptide may exacerbate diabetes-associated complications. In accordance with this, several studies suggest that C-peptide has beneficial effects in a number of diabetes-associated complications. C-peptide has been shown to prevent diabetic neuropathy by improving endoneural blood flow, preventing neuronal apoptosis and by preventing axonal swelling. In the vascular system, C-peptide has been shown to prevent vascular dysfunction in diabetic rats, and to possess anti-proliferative effects on vascular smooth muscle cells, which may prevent atherosclerosis. However, C-peptide depositions have been found in arteriosclerotic lesions of patients with hyperinsulinemic diabetes and C-peptide has been shown to induce pro-inflammatory mediators, such as nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2, indicating that C-peptide treatment could be associated with side-effects that may accelerate the development of diabetes-associated complications. This review provides a brief summary of recent research in the field and discusses potential beneficial and detrimental effects of C-peptide supplementation.Keywords: C-peptide, proinsulin, diabetes, cardiovascular

  17. Immunological studies on synthetic rat and guinea pig C-peptides

    International Nuclear Information System (INIS)

    Radioimmunoassay systems are developed for rat and guinea pig C-peptides, as part of a immunological study. The importance of using well-characterized antisera is indicated. Specific systems are established capable of discriminating between 2 kinds of rat C-peptides. (C.F.)

  18. Pregnancy-induced rise in serum C-peptide concentrations in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Rehfeld, Jens F; Pedersen-Bjergaard, Ulrik;

    2009-01-01

    OBJECTIVE: The purpose of this study was to investigate whether pregnancy induces increased insulin production as a marker of improved beta-cell function in women with long-term type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a prospective study of 90 consecutive pregnant women with type 1...... diabetes. At 8, 14, 21, 27, and 33 weeks blood samples were drawn for measurements of A1C, C-peptide, and serum glucose. C-peptide (detection limit: 6 pmol/l) was considered stimulated at a corresponding serum glucose concentration >or=5.0 mmol/l. GAD antibody concentration was determined at 8 and 33 weeks...... in 35 women. RESULTS: C-peptide concentrations gradually increased throughout pregnancy regardless of serum glucose concentrations in the 90 women with a median duration of diabetes of 17 years (range 1-36 years). Among 35 women with paired recordings of stimulated C-peptide, C-peptide production...

  19. A New Classification Plot for the C-Peptide Suppression Test.

    Directory of Open Access Journals (Sweden)

    Saddig C

    2002-01-01

    Full Text Available CONTEXT AND OBJECTIVE: To evaluate the C-peptide suppression test as a screening test in patients with symptoms of hypoglycemia as compared to the standard fasting test. DESIGN: Retrospective discriminant analysis of data from C-peptide suppression tests. SETTING: Clinical study. PATIENTS: Patients with insulinomas and patients without insulinomas but having symptoms compatible with hypoglycemia. INTERVENTIONS: The results from C-peptide suppression tests of 26 patients with insulinomas and 100 patients without insulinomas were compared. MAIN OUTCOME MEASURES: A classification plot which introduces two discriminant parameters for the C-peptide suppression test: the ratio of [blood glucose]/[C-peptide] at the lowest C-peptide concentration and mean glycemia during insulin infusion. RESULTS: In patients with insulinomas, minimal serum C-peptide levels were higher (1.81+/- 0.87 ng/mL; median 1.83 ng/mL; maximal suppression 37 +/- 24% of basal C-peptide levels as compared to patients without insulinoma (0.40 +/- 0.15 ng/mL; median 0.30 ng/mL; maximal suppression of 75 +/- 9%; P less than 0.001. Mean glycemia during the test was lower in patients with insulinomas (30.8 +/- 3.3 vs. 47.5 +/- 8.3 mg/dL; P less than 0.001 as was the [blood glucose]/[C-peptide] ratio (21.9 +/- 14.6 vs. 139.2 +/- 43.8; P less than 0.001. Discriminant analysis revealed a specificity of 96% to rule out the diagnosis of insulinoma at a 1% probability threshold with a sensitivity of 100%. CONCLUSIONS: We developed a new classification plot for the C-peptide suppression test in order to accurately identify those patients whose symptoms of hypoglycemia are not due to endogenous hyperinsulinemia/insulinomas. Thus, the need for fasting tests and hospitalization costs can be reduced.

  20. C-peptide protects against hyperglycemic memory and vascular endothelial cell apoptosis.

    Science.gov (United States)

    Bhatt, Mahendra Prasad; Lee, Yeon-Ju; Jung, Se-Hui; Kim, Yong Ho; Hwang, Jong Yun; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo

    2016-10-01

    C-peptide exerts protective effects against diabetic complications; however, its role in inhibiting hyperglycemic memory (HGM) has not been elucidated. We investigated the beneficial effect of C-peptide on HGM-induced vascular damage in vitro and in vivo using human umbilical vein endothelial cells and diabetic mice. HGM induced apoptosis by persistent generation of intracellular ROS and sustained formation of ONOO(-) and nitrotyrosine. These HGM-induced intracellular events were normalized by treatment with C-peptide, but not insulin, in endothelial cells. C-peptide also inhibited persistent upregulation of p53 and activation of mitochondrial adaptor p66(shc) after glucose normalization. Further, C-peptide replacement therapy prevented persistent generation of ROS and ONOO(-) in the aorta of diabetic mice whose glucose levels were normalized by the administration of insulin. C-peptide, but not insulin, also prevented HGM-induced endothelial apoptosis in the murine diabetic aorta. This study highlights a promising role for C-peptide in preventing HGM-induced intracellular events and diabetic vascular damage.

  1. C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    James A Shaw

    Full Text Available C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72 in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05. Reduction in albuminuria was also reported in the C-peptide group (p<0.05. In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001 reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05, glomerular volume (p<0.00001, and mesangial matrix area (p<0.00001 in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472.

  2. Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

    DEFF Research Database (Denmark)

    Henriksen, J H; Tronier, B; Bülow, J B

    1987-01-01

    Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular......, liver, and elsewhere in the approximate proportion 10%:65%:25%, whereas, C-peptide was removed by one half in kidney and the other half elsewhere. The overall metabolic clearance rates of insulin and C-peptide were estimated to be 15 and 4.5 mL/min/kg, respectively. The results indicate that the kidney...

  3. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study

    OpenAIRE

    Huus, Karina; Åkerman, Linda; Raustorp, Anders; Ludvigsson, Johnny

    2016-01-01

    Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the gene...

  4. Pathological consequences of C-peptide deficiency ininsulin-dependent diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ahmad Ghorbani; Reza Shafiee-Nick

    2015-01-01

    Diabetes is associated with several complicationssuch as retinopathy, nephropathy, neuropathy andcardiovascular diseases. Currently, insulin is the mainused medication for management of insulin-dependentdiabetes mellitus (type-1 diabetes). In this metabolicsyndrome, in addition to decrease of endogenous insulin,the plasma level of connecting peptide (C-peptide) is alsoreduced due to beta cell destruction. Studies in the pastdecade have shown that C-peptide is much more than abyproduct of insulin biosynthesis and possess differentbiological activities. Therefore, it may be possible thatC-peptide deficiency be involved, at least in part, in thedevelopment of different complications of diabetes. It hasbeen shown that a small level of remaining C-peptide isassociated with significant metabolic benefit. The purposeof this review is to describe beneficial effects of C-peptidereplacement on pathological features associated withinsulin-dependent diabetes. Also, experimental andclinical findings on the effects of C-peptide on wholebodyglucose utilization, adipose tissue metabolism andtissues blood flow are summarized and discussed. Thehypoglycemic, antilipolytic and vasodilator effects ofC-peptide suggest that it may contribute to fine-tuningof the tissues metabolism under different physiologic orpathologic conditions. Therefore, C-peptide replacementtogether with the classic insulin therapy may prevent,retard, or ameliorate diabetic complications in patientswith type-1 diabetes.

  5. C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shaw, James A; Shetty, Partha; Burns, Kevin D; Fergusson, Dean; Knoll, Greg A

    2015-01-01

    C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72) in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (psample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472). PMID:25993479

  6. Effect of C-Peptide on Diabetic Neuropathy in Patients with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Karin Ekberg

    2008-01-01

    Full Text Available Recent results indicate that proinsulin C-peptide, contrary to previous views, exerts important physiological effects and shows the characteristics of a bioactive peptide. Studies in type 1 diabetes, involving animal models as well as patients, demonstrate that C-peptide in replacement doses has the ability to improve peripheral nerve function and prevent or reverse the development of nerve structural abnormalities. Peripheral nerve function, as evaluated by determination of sensory nerve conduction velocity and quantitative sensory testing, is improved by C-peptide replacement in diabetes type 1 patients with early stage neuropathy. Similarly, autonomic nerve dysfunction is ameliorated following administration of C peptide for up to 3 months. As evaluated in animal models of type 1 diabetes, the improved nerve function is accompanied by reversal or prevention of nerve structural changes, and the mechanisms of action are related to the ability of C-peptide to correct diabetes-induced reductions in endoneurial blood flow and in Na+,K+-ATPase activity and modulation of neurotrophic factors. Combining the results demonstrates that C-peptide may be a possible new treatment of neuropathy in type 1 diabetes.

  7. pH-Dependent Interaction between C-Peptide and Phospholipid Bicelles

    Directory of Open Access Journals (Sweden)

    Sofia Unnerståle

    2012-01-01

    Full Text Available C-peptide is the connecting peptide between the A and B chains of insulin in proinsulin. In this paper, we investigate the interaction between C-peptide and phospholipid bicelles, by circular dichroism and nuclear magnetic resonance spectroscopy, and in particular the pH dependence of this interaction. The results demonstrate that C-peptide is largely unstructured independent of pH, but that a weak structural induction towards a short stretch of β-sheet is induced at low pH, corresponding to the isoelectric point of the peptide. Furthermore, it is demonstrated that C-peptide associates with neutral phospholipid bicelles as well as acidic phospholipid bicelles at this low pH. C-peptide does not undergo a large structural rearrangement as a consequence of lipid interaction, which indicates that the folding and binding are uncoupled. In vivo, local variations in environment, including pH, may cause C-peptide to associate with lipids, which may affect the aggregation state of the peptide.

  8. Low levels of C-peptide have clinical significance for established Type 1 diabetes

    Science.gov (United States)

    Kuhtreiber, W. M.; Washer, S. L. L.; Hsu, E.; Zhao, M.; Reinhold, P.; Burger, D.; Zheng, H.; Faustman, D. L.

    2015-01-01

    Aim To determine whether the low C-peptide levels (diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n=1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n=1273), as well as diabetic complications (n=324) and presence of hypoglycaemia (n=323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P=0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (Pdiabetes. PMID:26172028

  9. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Karina Huus

    Full Text Available To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity over time.A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linköping at age 8, and the same 107 children from Linköping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean.High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12 but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and β-cell load.Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing β-cells, might increase the risk for both type 1- and 2 diabetes.

  10. Discrepancy between plasma C-peptide and insulin response to oral and intravenous glucose

    DEFF Research Database (Denmark)

    Madsbad, S; Kehlet, H; Hilsted, J;

    1983-01-01

    Plasma insulin, proinsulin, and C-peptide responses to 25 g glucose orally and intravenously administered were measured in 10 healthy males. Plasma insulin response was higher during the oral load in accordance with the "incretin" concept. However, the actual amount of insulin secreted, as measured...... by the plasma C-peptide response, was similar during the two glucose loads. The higher plasma insulin response after oral glucose was not due to crossreactivity with proinsulin in the insulin assay. These results suggest that the higher plasma insulin response during an oral glucose load is due at...

  11. Insulin, not C-peptide (proinsulin), is present in crinophagic bodies of the pancreatic B-cell

    OpenAIRE

    1984-01-01

    We have obtained evidence by autoradiography and immunocytochemistry that mature secretory granules of the pancreatic B-cell gain access to a lysosomal compartment (multigranular or crinophagic bodies) where the secretory granule content is degraded. Whereas the mature secretory granule content shows both insulin and C-peptide (proinsulin) immunoreactivities, in crinophagic bodies only insulin, but not C- peptide, immunoreactivity was detectable. The absence of C-peptide (proinsulin) immunore...

  12. Development of SI-traceable C-peptide certified reference material NMIJ CRM 6901-a using isotope-dilution mass spectrometry-based amino acid analyses.

    Science.gov (United States)

    Kinumi, Tomoya; Goto, Mari; Eyama, Sakae; Kato, Megumi; Kasama, Takeshi; Takatsu, Akiko

    2012-07-01

    A certified reference material (CRM) is a higher-order calibration material used to enable a traceable analysis. This paper describes the development of a C-peptide CRM (NMIJ CRM 6901-a) by the National Metrology Institute of Japan using two independent methods for amino acid analysis based on isotope-dilution mass spectrometry. C-peptide is a 31-mer peptide that is utilized for the evaluation of β-cell function in the pancreas in clinical testing. This CRM is a lyophilized synthetic peptide having the human C-peptide sequence, and contains deamidated and pyroglutamylated forms of C-peptide. By adding water (1.00 ± 0.01) g into the vial containing the CRM, the C-peptide solution in 10 mM phosphate buffer saline (pH 6.6) is reconstituted. We assigned two certified values that represent the concentrations of total C-peptide (mixture of C-peptide, deamidated C-peptide, and pyroglutamylated C-peptide) and C-peptide. The certified concentration of total C-peptide was determined by two amino acid analyses using pre-column derivatization liquid chromatography-mass spectrometry and hydrophilic chromatography-mass spectrometry following acid hydrolysis. The certified concentration of C-peptide was determined by multiplying the concentration of total C-peptide by the ratio of the relative area of C-peptide to that of the total C-peptide measured by liquid chromatography. The certified value of C-peptide (80.7 ± 5.0) mg/L represents the concentration of the specific entity of C-peptide; on the other hand, the certified value of total C-peptide, (81.7 ± 5.1) mg/L can be used for analyses that does not differentiate deamidated and pyroglutamylated C-peptide from C-peptide itself, such as amino acid analyses and immunochemical assays.

  13. Evaluation of insulin and C-peptide in diabetic patients undergoing renal dialysis

    Directory of Open Access Journals (Sweden)

    P. T. Annamala

    2016-10-01

    Conclusions: There are alterations in the levels of insulin, c-peptide and the glycemic status in diabetic patients during dialysis. This significant reduction may affect glucose metabolism in diabetic patients on dialysis. Hence, glycemic status should be continuously monitored in these patients. [Int J Res Med Sci 2016; 4(10.000: 4579-4582

  14. 21 CFR 862.1135 - C-peptides of proinsulin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-peptides of proinsulin test system. 862.1135 Section 862.1135 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  15. Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Tronier, B; Bülow, J B

    1987-01-01

    Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular...

  16. C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Thomas Hach

    2008-01-01

    Full Text Available Aims/hypothesis. Data now indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. This study aimed to investigate the influence of C-peptide and fragments thereof on erythrocyte deformability and to elucidate the relevant signal transduction pathway. Methods. Blood samples from 23 patients with type 1 diabetes and 15 matched healthy controls were incubated with 6.6 nM of either human C-peptide, C-terminal hexapeptide, C-terminal pentapeptide, a middle fragment comprising residues 11–19 of C-peptide, or randomly scrambled C-peptide. Furthermore, red blood cells from 7 patients were incubated with C-peptide, penta- and hexapeptides with/without addition of ouabain, EDTA, or pertussis toxin. Erythrocyte deformability was measured using a laser diffractoscope in the shear stress range 0.3–60 Pa. Results. Erythrocyte deformability was impaired by 18–25% in type 1 diabetic patients compared to matched controls in the physiological shear stress range 0.6–12 Pa (P<.01–.001. C-peptide, penta- and hexapeptide all significantly improved the impaired erythrocyte deformability of type 1 diabetic patients, while the middle fragment and scrambled C-peptide had no detectable effect. Treatment of erythrocytes with ouabain or EDTA completely abolished the C-peptide, penta- and hexapeptide effects. Pertussis toxin in itself significantly increased erythrocyte deformability. Conclusion/interpretation. C-peptide and its C-terminal fragments are equally effective in improving erythrocyte deformability in type 1 diabetes. The C-terminal residues of C-peptide are causally involved in this effect. The signal transduction pathway is Ca2+-dependent and involves activation of red blood cell Na+,K+-ATPase.

  17. Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa

    International Nuclear Information System (INIS)

    Lower concentrations of the insulin–like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC. Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models. Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1st Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0). Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender

  18. Changes of serum leptin and c-peptide level in children with type 1 diabetic mellitus

    International Nuclear Information System (INIS)

    To deplore the relationship between leptin and c-peptide in children with type 1 diabetic mellitus (DM). The levels of serum leptin and c-peptide (C-P) in 65 type 1 DM children (including 31 before and after insulin treatment) and 30 normal controls were measured by radioimmunoassay (RIA). The results found that there was significant differences (P < 0.01) in leptin and C-P between DM children and normal controls, also in 31 DM children before and after treatment. It showed a positive correlation between leptin and C-P. The changes of the leptin/C-P ratio in DM children compared with normal controls and that before and after treatment were also significantly different. It suggested that leptin may have close relationship in the development, progress and the occurrence of complications in children with DM and also provide a new clue for their diagnosis treatment and complication occurrence

  19. The effect of oral and intravenous dextrose on C-peptide secretion in ponies.

    Science.gov (United States)

    de Laat, M A; van Haeften, J J; Sillence, M N

    2016-02-01

    Managing equine hyperinsulinemia is crucial for preventing laminitis, but our understanding of the mechanisms involved in insulin dysregulation in this species is incomplete. C-peptide is co-secreted with insulin but is resistant to hepatic metabolism and can be used to study insulin dysregulation. This study examined C-peptide secretion in serial blood samples collected after oral and i.v. dextrose (0.75 g/kg) administration to 9 ponies (BCS, 7.1 ± 0.5). The ponies were designated as hyperinsulinemic (HI) or normoinsulinemic (NI) responders before the study, using oral glucose tests and fasted glucose-to-insulin ratios, and responses were compared between the 2 groups. C-peptide concentrations increased ( < 0.01) rapidly from fasted levels after both oral and i.v. dextrose, with similar area under the concentration-time curve (AUC) for both tests and a significant correlation with AUC. The AUC was similar in HI and NI ponies after i.v. dextrose, indicating similar pancreatic capacity for both groups. However, for oral dextrose, the AUC and the AUC were markedly higher ( < 0.05) in the HI ponies, indicating a greater secretion rate of these peptides. Slower insulin clearance might have also contributed to the larger AUC in HI ponies, but this hypothesis requires further investigation with specific measures of hepatic insulin clearance. PMID:27065127

  20. Urinary C-peptide of insulin as a non-invasive marker of energy balance in wild orangutans.

    Science.gov (United States)

    Emery Thompson, Melissa; Knott, Cheryl D

    2008-04-01

    Assessment of energetic condition is a critical tool for behavioral and reproductive ecologists. However, accurate quantification of energy intake and expenditure is labor-intensive, and it can be problematic for field scientists to obtain regular data on individual animals. C-peptide, a polypeptide segment of the proinsulin molecule that is secreted along with insulin in an equimolar relationship, can be measured in urine, and thus offers a potential means for the non-invasive assessment of energy balance in wild animals. Here, we validate C-peptide for the quantification of energetic condition, with specific application to wild orangutans (Pongo pygmaeus). We determined that application of urine to filter paper results in significantly lower C-peptide recoveries versus fresh samples. However, concentrations in filter paper samples were significantly correlated with fresh urine and were stable over various storage conditions and durations. We compared the C-peptide concentrations from wild orangutan urine samples with three independent measures of energetic condition: ketone bodies (urinalysis), caloric intake (nutritional biochemistry), and food availability (phenology). As expected, C-peptide concentrations were significantly lower in samples that tested positive for ketones in the field. Monthly average C-peptide concentrations of both male and female orangutans were significantly correlated with monthly determinations of energy intake and food availability. Therefore, we conclude that the collection and preservation of urine samples for C-peptide analysis are feasible under most field conditions and, in this species, presents a useful tool for assessing changes in energy balance. PMID:18255067

  1. Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Sung-Tae Kim

    2011-02-01

    Full Text Available BackgroundRecent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM patients.MethodsData was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed.ResultsA simple correlation was found between basal C-peptide and components of metabolic syndrome (MS. Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III of the National Cholesterol Education Program's (NCEP's, World Health Organization (WHO, and the International Diabetes Federation (IDF criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029. The multiple regression analysis between intima-media thickness (IMT and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043, while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226.ConclusionBasal C-peptide is related to cardiovascular predictors (IMT of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.

  2. Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus.

    OpenAIRE

    Forst, T; Kunt, T; Pohlmann, T.; Goitom, K; Engelbach, M; Beyer, J.; Pfützner, A.

    1998-01-01

    19 insulin-dependent diabetes mellitus (IDDM) patients participated in a randomized double-blind crossover investigation to investigate the impact of human C-peptide on skin microvascular blood flow. The investigation was also carried out with 10 healthy volunteers. Blood pressure, heart rate, blood sugar, and C-peptide levels were monitored during a 60-min intravenous infusion period of C-peptide (8 pmol kg-1 min-1) or saline solution (154 mmol liter-1 NaCl), and 30 min after stopping the in...

  3. Sensitivity and reproducibility of urinary C-peptide as estimate of islet B-cell function in insulin-treated diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Faber, O K;

    1989-01-01

    The aims of the present study were to evaluate the ability of urinary C-peptide determination to demonstrate presence of residual insulin secretion, and to evaluate the reproducibility of urinary C-peptide excretion in 125 insulin-treated diabetic patients. C-peptide was determined in two consecu...

  4. Study on the relationship between fasting blood sugar and GH, C-peptide levels in patients with DM2

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between fasting blood sugar (FBG) and growth hormone (GH), C-peptide (CP) levels in patients with type II diabetes mellitus (DM2). Methods: Serum fasting glucose (with biochemical method) GH, C-peptide (with RIA) levels were measured in 64 patients with DM2 and 31 controls. Results: In the 64 patients, 40 were relatively well-controlled (FBG <9.0mmol/L) and 24 were relatively poorly-controlled (FBG ≥ 9.0mmol/L), The serum GH levels in the poorly controlled group were significantly higher than those in the well-controlled group (P<0.01), which, in turn, were significantly higher than those in the controls (P<0.01). The reverse was exactly true for the C-peptide levels. Conclusion: The higher GH and lower C-peptide levels might be a contributory, cause of the inadequate control in these patients. (authors)

  5. Clinical significance of detection of insulin and C peptide in type 2 diabetic patients by chemiluminescence immunoassay

    International Nuclear Information System (INIS)

    To explore the clinical significance of insulin and C peptide in type 2 diabetic patients, the serum insulin and C peptide levels in 50 type 2 diabetics patients and 30 health controls were determined by chemiluminescence immunoassay. The results showed that the serum levels of insulin and C peptide in patients were significantly higher than that of healthy controls (P<0.05). The peak level of blood sugar appeared at 1 hour after meals in healthy controls, while in patients appeared at 2 hours and didn't return to normal at 3 hours. The serum insulin and C peptide levels could be used to determine the function of islet β cells and to guide clinical treatment. (authors)

  6. The Effects of C-peptide on Type 1 Diabetic Polyneuropathies and Encephalopathy in the BB/Wor-rat

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    Anders A. F. Sima

    2008-01-01

    Here the effects of C-peptide replenishment will be extensively described as they pertain to DPN and diabetic encephalopathy, underpinning its beneficial effects on neurological complications in type 1 diabetes.

  7. Role of C-peptide in Altered Lipid Profile among Apparently Healthy Adults of Vijayapura City, Karnataka

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    Chandrahas M.Kulkarni

    2016-04-01

    Full Text Available Background: C-peptide is produced in equimolar concentration during insulin production as inactive molecule by beta islet cells of Langerhans. C-peptide is most useful biomarker of endogenous insulin production. Aim and Objectives: To predict metabolic syndrome in advance by estimation of C-peptide and lipid profile in healthy adults. Material and Methods: Serum C-peptide, fasting blood glucose and lipid profile of 128 healthy individuals were estimated. Adults in the age group of 18 to 60 years of both sexes were included in study. Results: C-peptide levels were increased in 27%, Serum cholesterol in 30%, LDL Cholesterol in 55% and triglyceride levels in 21% of healthy individuals. Significant correlation was observed between C peptide, age, serum cholesterol, LDL and cholesterol LDL ratio in male subjects only. In our study group most of the subjects (both males and females fell in overweight group. Conclusion: Cpeptide level and lipid profile may be considered as useful biomarkers to predict type 2 diabetes mellitus in advance, possibly due to insulin resistance.

  8. C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a modelistic study.

    Directory of Open Access Journals (Sweden)

    Francesco Di Nardo

    Full Text Available A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT was performed in seven Zucker fatty rats (ZFR, 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR. The minimal model of C-peptide (CPMM, originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM. Our results showed that the present CPMM-based interpretation of data is able to: 1 provide a suitable fit of C-Peptide data; 2 achieve a satisfactory estimation of parameters of interest 3 quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t, and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф(1, second-phase, Ф(2, and steady-state, Ф(ss, never assessed in Zucker rats before; 4 detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation.

  9. Insulin and C peptide response, and antibody levels in hepatitis C related chronic liver disease

    International Nuclear Information System (INIS)

    Objective: Patients with cirrhosis due to hepatitis C (HC) have an increased prevalence of diabetes mellitus. The pathogenic mechanism by which HC predisposes to DM is not clear. The objective of this study was to determine the insulin and C-peptide response to 75 gram oral glucose load and measure anti phospholipid antibody levels in patients with chronic liver disease due to HC. Design: a prospective study. Place and duration of study: This study was conducted at the department of medicine, Jinnah postgraduate medical centre over period of three months. Subjects and methods: An analytical case control study was carried out on 37 patients (m-18,f=19); none of these patients had received interferon. They were divided into four groups: (a) HC cirrhosis with DM (n=9 ), (b) HC cirrhosis without DM (n=11), (c) hepatitis B (HB) cirrhosis without DM (n=7), (d) chronic hepatitis C without DM (n=10). Group C and D were taken as controls. Fasting blood samples were taken and repeated after 2 hours of 75 gram oral glucose load (2 h PG). Result: mean ages of group A,B,C and D were (yr +- SD) 51.3 +- 7.6,48.9 +- 2.4, 33.7 +-10.8 and 31.7 +- 8.8 respectively. There was no statistically significant difference in the age, Pugh score and body mass index of HC cirrhotic patients with and without DM. Patients of group A had higher fasting and 2 h PG glucose levels (P=0.003 and 0.000) and higher fasting insulin level (p=0.045). However, increments in insulin and c peptide levels 2 h PG were much less (p=0.048 and 0.003). HB cirrhotics without diabetes (group C behaved just like HC cirrhotic without diabetes (group B). Patients of group D had normal glucose tolerance and insulin and C peptide levels. All four groups had normal anti phospholipid antibody levels. Conclusion: Patients with cirrhosis due to HC nd HB show evidence of glucose intolerance in spite of hyperinsulinaemia probably due to insulin resistance. HC cirrhotics with diabetes have fasting hyperglycemia in spite of

  10. Expression and Purification of C-Peptide Containing Insulin Using Pichia pastoris Expression System.

    Science.gov (United States)

    Baeshen, Mohammed N; Bouback, Thamer A F; Alzubaidi, Mubarak A; Bora, Roop S; Alotaibi, Mohammed A T; Alabbas, Omar T O; Alshahrani, Sultan M; Aljohani, Ahmed A M; Munshi, Rayan A A; Al-Hejin, Ahmed; Ahmed, Mohamed M M; Redwan, Elrashdy M; Ramadan, Hassan A I; Saini, Kulvinder S; Baeshen, Nabih A

    2016-01-01

    Increase in the incidence of Insulin Dependent Diabetes Mellitus (IDDM) among people from developed and developing countries has created a large global market for insulin. Moreover, exploration of new methods for insulin delivery including oral or inhalation route which require very high doses would further increase the demand of cost-effective recombinant insulin. Various bacterial and yeast strains have been optimized to overproduce important biopharmaceuticals. One of the approaches we have taken is the production of recombinant human insulin along with C-peptide in yeast Pichia pastoris. We procured a cDNA clone of insulin from Origene Inc., USA. Insulin cDNA was PCR amplified and cloned into yeast vector pPICZ-α. Cloned insulin cDNA was confirmed by restriction analysis and DNA sequencing. pPICZ-α-insulin clone was transformed into Pichia pastoris SuperMan 5 strain. Several Zeocin resistant clones were obtained and integration of insulin cDNA in Pichia genome was confirmed by PCR using insulin specific primers. Expression of insulin in Pichia clones was confirmed by ELISA, SDS-PAGE, and Western blot analysis. In vivo efficacy studies in streptozotocin induced diabetic mice confirmed the activity of recombinant insulin. In conclusion, a biologically active human proinsulin along with C-peptide was expressed at high level using Pichia pastoris expression system. PMID:27579308

  11. Measurement of insulin and C-peptide excitatory test levels in gestational diabetes mellitus

    International Nuclear Information System (INIS)

    To investigate the function of islet β cells in patients with gestational diabetes mellitus (GDM), serum insulin and C-peptide (C-P) excitatory test levels were measured dynamically by radioimmunoassay in 41 patients with GDM and 30 normal pregnant controls. The results showed that there were significant difference in insulin and C-peptide excitatory test levels between normal pregnancy for 32-40 weeks and patients with GDM (P < 0.001). The secretory peak of insulin occurred at 60 min in normal pregnancy, while at 120 min in patients with GDM, and the recovery postponed in patients with GDM. The peak time for C-P was just as same as that of insulin, but the peak error for C-P between normal pregnant controls and patients with GDM was more larger than that for insulin and it recovered more slowly. It suggested that majority of islet β cells in patients with GDM were good enough for response to islet resistance factors and big stress from pregnancy, and also suggested a relation between pregnancy and islet β cells function

  12. Expression and Purification of C-Peptide Containing Insulin Using Pichia pastoris Expression System

    Directory of Open Access Journals (Sweden)

    Mohammed N. Baeshen

    2016-01-01

    Full Text Available Increase in the incidence of Insulin Dependent Diabetes Mellitus (IDDM among people from developed and developing countries has created a large global market for insulin. Moreover, exploration of new methods for insulin delivery including oral or inhalation route which require very high doses would further increase the demand of cost-effective recombinant insulin. Various bacterial and yeast strains have been optimized to overproduce important biopharmaceuticals. One of the approaches we have taken is the production of recombinant human insulin along with C-peptide in yeast Pichia pastoris. We procured a cDNA clone of insulin from Origene Inc., USA. Insulin cDNA was PCR amplified and cloned into yeast vector pPICZ-α. Cloned insulin cDNA was confirmed by restriction analysis and DNA sequencing. pPICZ-α-insulin clone was transformed into Pichia pastoris SuperMan5 strain. Several Zeocin resistant clones were obtained and integration of insulin cDNA in Pichia genome was confirmed by PCR using insulin specific primers. Expression of insulin in Pichia clones was confirmed by ELISA, SDS-PAGE, and Western blot analysis. In vivo efficacy studies in streptozotocin induced diabetic mice confirmed the activity of recombinant insulin. In conclusion, a biologically active human proinsulin along with C-peptide was expressed at high level using Pichia pastoris expression system.

  13. Relationship between Body Mass Index, C-Peptide, and Delta-5-Desaturase Enzyme Activity Estimates in Adult Males

    Science.gov (United States)

    Pickens, C. Austin; Matsuo, Karen H.; Fenton, Jenifer I.

    2016-01-01

    Obesity, in particular abdominal obesity, alters the composition of plasma and tissue fatty acids (FAs), which contributes to inflammation and insulin resistance. FA metabolism is modulated by desaturases and may affect adipokine and insulin secretion. Therefore, we examined relationships between adipokines, a marker of insulin production, and plasma FA desaturase enzyme activity estimates (EAEs) in obesity. Plasma phospholipid (PPL) FAs were isolated from 126 males (ages 48 to 65 years), derivatized, and analyzed using gas chromatography. Delta-6 desaturase (D6D) and delta-5 desaturase (D5D) EAEs were calculated as the ratio of PPL 20:3/18:2 and 20:4/20:3, respectively. In body mass index (BMI) and waist circumference (WC) adjusted polytomous logistic regression analyses, PPL FAs and FA desaturase EAEs were associated with C-peptide and adiponectin. Individuals with elevated D6D EAEs were less likely (OR 0.33) to have serum adiponectin concentrations > 5.37 μg/mL, compared with adiponectin concentrations ≤ 3.62 μg/mL. Individuals with increased D5D EAEs were less likely (OR 0.8) to have C-peptide concentrations ≥ 3.32 ng/mL, and > 1.80 and ≤ 3.29 ng/mL, compared with those with C-peptide ≤ 1.76 ng/mL. The proinflammatory cytokine tumor necrosis factor-α (TNF- α) was positively associated with C-peptide, but TNF- α was not associated with the D5D EAE. C-peptide and adiponectin concentrations are associated with specific PPL FAs and FA desaturase EAEs. The relationship between C-peptide concentrations and D5D EAEs remained significant after adjusting for BMI, WC, and TNF-α. Thus, future research should investigate whether D5D inhibition may occur through a C-peptide mediated pathway. PMID:27023786

  14. 18F-Labeled proinsulin connecting peptide (C-peptide): In vivo distribution and pharmacokinetics using PET

    International Nuclear Information System (INIS)

    C-peptide, produced and released in equimolar amounts with insulin, was previously considered biologically inactive. Administration to type 1 (insulin-dependent) diabetes mellitus (DM) patients has, however, indicated that C-peptide exerts a number of beneficial effects, improving long-term complications of type 1 DM on e.g. renal and nerve function (Wahren, Am J Physiol Endocrinol Metab 278: E759, 2000). Aim: To evaluate biodistribution and regional pharmacokinetics in humans using the 18F-labeled C-peptide and positron emission tomography. Materials and Methods: Five, fasting, male IDDM patients were scanned after injection of N-4-[18F]fluorobenzoyl-C-peptide. Dynamic scans over kidneys (4 pat: 2 no-carrier-added (n.c.a.); 2 carrier C-peptide added (c.a.)) and heart (1 pat, n.c.a) and static scans (n.c.a) over body segments (2 pat), CNS and urinary bladder were performed. Plasma radioactivity was also measured. Results: PET images showed predominant distribution of radioactivity to the kidneys (renal cortex 7% of injected dose (i.d.) at peak). Distinguishable amounts of radioactivity were also observed in heart, lungs and liver, but not in CNS at late times. Low amounts were observed in what was presumed to be pancreas. Uptake in total muscle, based on concentrations in a skeletal muscle ROI at 10-75 min, could account for up to 15% i.d. Radioactivity was excreted to the urinary bladder. Time-radioactivity curves for renal cortex peaked within the first 6 min and then decreased to ca 0.01±0.002% i.d./mL at 15 min. Radioactivity peaked in the second time frame (≤ 4 min) in liver and in the first time frame (≤ 2 min) in other organs and plasma. Washout for all organs and for plasma was biphasic. The kinetics in the renal cortex were different when carrier C-peptide was co-injected. Conclusion: The main distribution to the kidneys observed here is consistent with previous findings on C-peptide's catabolism and it's documented effects on renal function. This PET

  15. Diurnal Variations in Serum Glucose, Insulin and C-Peptide of Normal Korean Adults

    International Nuclear Information System (INIS)

    It is already well known that many factors are involved in maintaining normal blood glucose level. The amount and components of meal are also thought to be some of the factors which affect the blood glucose and insulin levels. It is reported that as for Koreans sugar takes up over 75% out of 2,098 kcal, the average daily calorie intake per adult. It implies that Koreans take a high-sugar diet compared with Westerners who take 40-50% of sugar out of their total average daily calorie. For the purpose of studying diurnal variations in serum glucose, insulin and C-peptide of normal Koreans adults based on ordinary Korean diet, we selected 13 normal Korean male adults and divided them into two groups, Group I (7 persons) and Group II (6 persons). We put Group I on 3,100 kcal and 75% sugar diet, and Group II on 2,100 kcal and 69% sugar diet per day for over 4 days. Serum glucose, insulin and C-peptide were checked every 30 minutes or every hour throughout 2 hour. Results are as follows: 1. As for serum glucose level, in the preprandial fasting state in the morning, mean±S.D. of Group I was 91.1±3.2 mg%, while that of Group II is 82.5±4.4 mg%. Both groups showed peaks of increased glucose level t postprandial 1 hour after each meal. The peak returned to the level shown during the fasting state at postprandial 1 hour after breakfast while the relatively high glucose levels were maintained respectively even for 2 or 3 hours after lunch and dinner. 2. As for serum insults level, Group I showed mean±S.D. of 14.7±3.0 μU/ml while Group II shows that of 7.0±2.6 μU/ml in the fasting state. Group I particularly showed the largest peak from preprandial a half or one and half an hour to postprandial one hour of lunch, and made relatively small peaks (47.7±10.8 μU/ml) at postprandial 1 hour after breakfast and dinner. No such large peak was marked in Group II, though it showed relatively similar patterns of peak after each meal. 3. As for C-peptide, in the fasting state

  16. The C-peptide response to a standard mixed meal in a group of Brazilian type 1 diabetic patients

    Directory of Open Access Journals (Sweden)

    Pozzan R.

    1997-01-01

    Full Text Available In order to analyze the different parameters used in the interpretation of C-peptide response in a functional test, we compared a group of 26 type 1 diabetics aged 21.1 ± 8.2 years, with a diabetes duration of 7.9 ± 6.7 months, with a group of 24 non-diabetic subjects aged 25.0 ± 4.4 years. A standard mixed meal of 317 kcal was used as a stimulus. Blood sampling for C-peptide determinations was performed at regular intervals. Although all the studied C-peptide variables were significantly lower in the diabetic group (P<0.0001, some overlapping of parameters was observed between the two groups. The highest degree of overlapping was found for basal value (BV (30.8% and percent increase (42.31%, and the lowest for incremental area, absolute increase, peak value (PV (3.8%, and total area (7.7% (c2 = 31.6, P<0.0001. We did not observe a definite pattern in the time of maximum response among the 21 diabetics who showed an increase in C-peptide levels after the stimulus. In this group, however, there was a highly significant number of late responses (120 min (c2 = 5.7, P<0.002. Although BV showed a significant correlation with PV (rS = 0.95, P<0.0001, the basal levels of C-peptide did not differentiate the groups with and without response to the stimulus. We conclude that the diabetic group studied showed delayed and reduced C-peptide responses, and that the functional test can be an important tool for the evaluation of residual ß cell function.

  17. Effects of Vitamin D Supplementation on C-peptide and 25-hydroxyvitamin D Concentrations at 3 and 6 Months

    OpenAIRE

    Chandler, Paulette D.; Giovannucci, Edward L.; Scott, Jamil B.; Bennett, Gary G.; Ng, Kimmie; Chan, Andrew T.; Bruce W Hollis; Rifai, Nader; Emmons, Karen M.; Fuchs, Charles S.; Drake, Bettina F.

    2015-01-01

    The link between African-Americans’ disproportionate rates of diabetes, obesity and vitamin D deficiency may be marked by C-peptide as an indicator of insulin secretion. We hypothesize that vitamin D supplementation will increase C-peptide, a marker of insulin secretion. During 3 winters from 2007-2010, 328 healthy African-Americans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. The di...

  18. Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis

    Science.gov (United States)

    The objective of this study was to test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. We analyzed 607 children aged diabetes after ex...

  19. Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

    Science.gov (United States)

    Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

    2012-01-01

    We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

  20. Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis

    Science.gov (United States)

    The objective of this study was to test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after ex...

  1. C peptide and insulin releasing RIA test for the investigation of β cell function in diabetic patients

    International Nuclear Information System (INIS)

    Results of C-peptide releasing RIA test in 15 normals, and 100 diabetes were summarized and compared with glucose tolerance test and serum insulin for investigating the characteristics in different types of diabetes and evaluating the functional state of islet β cell. In 36 cases of IDDM the fasting blood sugar was significantly increased, and further elevated after eating of bread, but its peak time delay in 2 hours (normalin 1 hour). The level of basal C-peptide is very low, but shows slightly weak on no response after bread stimulating test, all of this denotes that β cell function of islets severely injured. The increasing of fasting blood sugar in 64 cases of NIDDM was lower than those of IDDM. Fasting C-peptide and insulin was normal or increased, their peak value increased after bread stimulation with peak time delayed also at 2 hours. Above results demonstrated that the function of islets B cell decreased but not fully deprived. It is concluded that C-peptide and insulin stimulating test, together with OGTT can accurately assess the islets β cell function, and also have important significance in the pathogenesis, classification and staging, prognostic evaluation and monitoring of therapeutic effects in diabetes

  2. Socioecological correlates of energy balance using urinary C-peptide measurements in wild female mountain gorillas.

    Science.gov (United States)

    Grueter, Cyril C; Deschner, Tobias; Behringer, Verena; Fawcett, Katie; Robbins, Martha M

    2014-03-29

    Maintaining a balanced energy budget is important for survival and reproduction, but measuring energy balance in wild animals has been fraught with difficulties. Female mountain gorillas are interesting subjects to examine environmental correlates of energy balance because their diet is primarily herbaceous vegetation, their food supply shows little seasonal variation and is abundant, yet they live in cooler, high-altitude habitats that may bring about energetic challenges. Social and reproductive parameters may also influence energy balance. Urinary C-peptide (UCP) has emerged as a valuable non-invasive biomarker of energy balance in primates. Here we use this method to investigate factors influencing energy balance in mountain gorillas of the Virunga Volcanoes, Rwanda. We examined a range of socioecological variables on energy balance in adult females in three groups monitored by the Karisoke Research Center over nine months. Three variables had significant effects on UCP levels: habitat (highest levels in the bamboo zone), season (highest levels in November during peak of the bamboo shoot availability) and day time (gradually increasing from early morning to early afternoon). There was no significant effect of reproductive state and dominance rank. Our study indicates that even in species that inhabit an area with a seemingly steady food supply, ecological variability can have pronounced effects on female energy balance.

  3. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells

    DEFF Research Database (Denmark)

    Galuska, Dana; Pirkmajer, Sergej; Barres, Romain;

    2011-01-01

    Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in...

  4. Nutritional Factors and Preservation of C-Peptide in Youth With Recently Diagnosed Type 1 Diabetes

    Science.gov (United States)

    Mayer-Davis, Elizabeth J.; Dabelea, Dana; Crandell, Jamie L.; Crume, Tessa; D’Agostino, Ralph B.; Dolan, Lawrence; King, Irena B.; Lawrence, Jean M.; Norris, Jill M.; Pihoker, Catherine; The, Natalie

    2013-01-01

    OBJECTIVE To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP). RESULTS In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002). CONCLUSIONS Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes. PMID:23801797

  5. Proinsulin C-peptide antagonizes the profibrotic effects of TGF-beta1 via up-regulation of retinoic acid and HGF-related signaling pathways.

    Science.gov (United States)

    Hills, Claire E; Willars, Gary B; Brunskill, Nigel J

    2010-04-01

    Novel signaling roles for C-peptide have recently been discovered with evidence that it can ameliorate complications of type 1 diabetes. Here we sought to identify new pathways regulated by C-peptide of relevance to the pathophysiology of diabetic nephropathy. Microarray analysis was performed to identify genes regulated by either C-peptide and/or TGF-beta1 in a human proximal tubular cell line, HK-2. Expression of retinoic acid receptor beta (RARbeta), hepatocyte growth factor (HGF), cellular retinoic acid-binding protein II (CRABPII), vimentin, E-cadherin, Snail, and beta-catenin was assessed by immunoblotting. The cellular localization of vimentin and beta-catenin was determined by immunocytochemistry. Changes in cell morphology were assessed by phase contrast microscopy. Gene expression profiling demonstrated differential expression of 953 and 1458 genes after C-peptide exposure for 18 h or 48 h, respectively. From these, members of the antifibrotic retinoic acid (RA)- and HGF-signaling pathways were selected. Immunoblotting demonstrated that C-peptide increased RARbeta, CRABPII, and HGF. We confirmed a role for RA in reversal of TGF-beta1-induced changes associated with epithelial-mesenchymal transition, including expression changes in Snail, E-cadherin, vimetin, and redistribution of beta-catenin. Importantly, these TGF-beta1-induced changes were inhibited by C-peptide. Further, effects of TGF-beta1 on Snail and E-cadherin expression were blocked by HGF, and inhibitory effects of C-peptide were removed by blockade of HGF activity. This study identifies a novel role for HGF as an effector of C-peptide, possibly via an RA-signaling pathway, highlighting C-peptide as a potential therapy for diabetic nephropathy. PMID:20197308

  6. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

    Science.gov (United States)

    Hills, Claire E; Al-Rasheed, Nawal; Al-Rasheed, Nouf; Willars, Gary B; Brunskill, Nigel J

    2009-03-01

    The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy. PMID:19091788

  7. Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study

    OpenAIRE

    Oram, Richard A.; Rawlingson, Andrew; Shields, Beverley M; Bingham, Coralie; Besser, Rachel E. J.; McDonald, Tim J.; Knight, Bridget A; Hattersley, Andrew T

    2013-01-01

    Objectives The current assessment of insulin resistance (IR) in epidemiology studies relies on the blood measurement of C-peptide or insulin. A urine C-peptide creatinine ratio (UCPCR) can be posted from home unaided. It is validated against serum measures of the insulin in people with diabetes. We tested whether UCPCR could be a surrogate measure of IR by examining the correlation of UCPCR with serum insulin, C-peptide and HOMA2 (Homeostasis Model Assessment 2)-IR in participants without dia...

  8. The Association between Newborn Regional Body Composition and Cord Blood Concentrations of C-Peptide and Insulin-Like Growth Factor I.

    Directory of Open Access Journals (Sweden)

    Emma M Carlsen

    Full Text Available Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I. Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I.We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA within 48 hours of birth.Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52% infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001. Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001 and IGF-I (p = 0.004.Peripheral fat tissue accumulation was associated with cord blood C-peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I.

  9. The role of insulin C-peptide in the coevolution analyses of the insulin signaling pathway: a hint for its functions.

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    Full Text Available As the linker between the A chain and B chain of proinsulin, C-peptide displays high variability in length and amino acid composition, and has been considered as an inert byproduct of insulin synthesis and processing for many years. Recent studies have suggested that C-peptide can act as a bioactive hormone, exerting various biological effects on the pathophysiology and treatment of diabetes. In this study, we analyzed the coevolution of insulin molecules among vertebrates, aiming at exploring the evolutionary characteristics of insulin molecule, especially the C-peptide. We also calculated the correlations of evolutionary rates between the insulin and the insulin receptor (IR sequences as well as the domain-domain pairs of the ligand and receptor by the mirrortree method. The results revealed distinctive features of C-peptide in insulin intramolecular coevolution and correlated residue substitutions, which partly supported the idea that C-peptide can act as a bioactive hormone, with significant sequence features, as well as a linker assisting the formation of mature insulin during synthesis. Interestingly, the evolution of C-peptide exerted the highest correlation with that of the insulin receptor and its ligand binding domain (LBD, implying a potential relationship with the insulin signaling pathway.

  10. Association of serum C-peptide concentrations with cancer mortality risk in pre-diabetes or undiagnosed diabetes.

    Directory of Open Access Journals (Sweden)

    Chih-Neng Hsu

    Full Text Available BACKGROUND: Known associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up. METHODS: The cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics. Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006. A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c, C-peptide, insulin like growth factor (IGF-1, IGF binding protein 3 (IGFBP3 and estimated insulin resistance. RESULTS: A total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02-3.77 and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31-5.36 were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality. CONCLUSION: C-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.

  11. Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: potential role of C-peptide.

    Science.gov (United States)

    Chen, Guanjie; Adeyemo, Adebowale; Zhou, Jie; Chen, Yuanxiu; Huang, Hanxia; Doumatey, Ayo; Lashley, Kerrie; Agyenim-Boateng, Kofi; Eghan, Benjamin A; Acheampong, Joseph; Fasanmade, Olufemi; Johnson, Thomas; Okafor, Godfrey; Oli, Johnnie; Amoah, Albert; Rotimi, Charles

    2007-12-01

    C-peptide is a substance that the pancreas releases into the circulation in equimolar amounts to insulin and has demonstrated important physiological effects which relate to the vascular field, in particular the microcirculation. For this analysis, we included 321 full and 36 half sibling pairs affected with type 2 diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a total of 691 persons. Variance components based on multipoint linkage approach as implemented in SOLAR were performed for log C-peptide. Significant linkage evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p-value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score 2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p-value=0.0094). Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23. In conclusion, we identified four major genetic loci (10q23, 4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with T2D.

  12. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells.

    Directory of Open Access Journals (Sweden)

    Dana Galuska

    Full Text Available BACKGROUND: Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC in control and hyperglycemic conditions. METHODOLOGY/PRINCIPAL FINDINGS: HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86Rb(+ uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM. DNA binding activity was determined by electrical mobility shift assay (EMSA. Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase α(1-subunit protein expression, accompanied with increase in (86Rb(+ uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase α(1-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, but not 10 nM of C-peptide increased PKCε phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6, concomitant with Na,K-ATPase α(1-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase α(1-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing. CONCLUSIONS/SIGNIFICANCE: Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C-peptide. Most likely C-peptide stimulates sodium pump expression via activation of ZEB, a transcription

  13. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Hansen, L.; Herder, C.;

    2008-01-01

    OBJECTIVE: We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1 beta, IL-6, and CCL2, and tumor necrosis factor-alpha with beta-cell function, metabolic status, and clinical remission in patients...... association of IL-1 beta with C-peptide after 1 month (P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12 months (P < 0.05) and positively correlated with A1C after 1 month (P = 0.0004). Proinflammatory IL-6 was elevated in patients with...... improving beta-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes. The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models into the human situation in vivo Udgivelsesdato: 2008/4...

  14. Improvement of C peptide zero BMI 24-34 diabetic patients after tailored one anastomosis gastric bypass (BAGUA

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    M. Garcia-Caballero

    2013-01-01

    Full Text Available Background: Although bariatric surgery proved to be a very effective method in the treatment of patients in whose pancreas still produce insulin (type 2 diabetes, the accompanied metabolic syndrome and their diabetes complications, there is no information on the effect of this type of surgery in BMI24-34 patients when pancreas do not produce insulin at all (type 1, LADA and long term evolution type 2 diabetes among others. Patients and methods: We report preliminary data of a serie of 11 patients all with a C-peptide values below 0.0 ng/ml. They were followed for 6 to 60 months (mean 19 months after surgery. We studied the changes in glycemic control, evolution of the metabolic syndrome and diabetes complications after one anastomosis gastric bypass (BAGUA. Results: All values relative to glycemic control were improved HbA1c (from 8.9 ± 0.6 to 6.7 ± 0.2%, FPG (Fasting Plasma Glucose [from 222.36 ± 16.87 to 94 ± 5 (mg/dl] as well as the daily insulin requirement of rapid (from 40.6 ± 12.8 to 0 (U/d and long-lasting insulin (from 41.27 ± 7.3 U/day to 15.2 ± 3.3 U/day. It resolved 100% of the metabolic syndrome diseases as well as severe hypoglycaemia episodes present before surgery and improved some serious complications from diabetes like retinopathy, nephropathy, neuropathy, peripheral vasculopathy and cardiopathy. Conclusions: Tailored one anastomosis gastric bypass in BMI 24-34 C peptide zero diabetic patients eliminated the use of rapid insulin, reduced to only one injection per day long-lasting insulin and improved the glycemic control. After surgery disappear metabolic syndrome and severe hypoglycaemia episodes and improves significantly retinopathy, neuropathy, nephropathy, peripheral vasculopathy and cardiopathy.

  15. A novel glucokinase gene mutation and its effect on glycemic/C-peptide fluctuations in a patient with maturity-onset diabetes of the young type 2.

    Science.gov (United States)

    Loomba-Albrecht, Lindsey A; Jame, Maryam; Bremer, Andrew A

    2010-03-01

    Maturity-onset diabetes of the young (MODY) is a group of disorders accounting for 2-5% of diabetes; MODY2 is caused by inactivating GCK mutations. We report a case of MODY2 caused by a novel GCK mutation and demonstrate differential glycemic/C-peptide responses to treatment with insulin, no medication, and an oral sulfonylurea. PMID:20015564

  16. Effect of maternal lipid profile, C-peptide, insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns

    Institute of Scientific and Technical Information of China (English)

    Ruo-Lin Hou; Huan-Huan Zhou; Xiao-Yang Chen; Xiu-Min Wang; Jie Shao; Zheng-Yan Zhao

    2014-01-01

    Background: Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns. Methods: This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns. Results: Maternal TG, C-peptide, insulin and HbA1c levels were signifi cantly higher in the LGA group than in the AGA group (P Conclusion: High maternal TG level during late pregnancy is signifi cantly associated with LGA newborns.

  17. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); J.L.D. Wattimena (Josias); T. Rietveld (Trinet); J.N.I. van Miert (Joram); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2016-01-01

    textabstractThe purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January

  18. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P oral (Cau r = -0.61, P indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.

  19. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C;

    1992-01-01

    Synthetic peptides representing unique sequences in rat proinsulin C-peptide I and II were used to generate highly specific antisera, which, when applied on sections of normal rat pancreas, confirm a homogeneous coexpression of the two C-peptides in all islet beta-cells. Insulin gene expression...... of transcription.(ABSTRACT TRUNCATED AT 250 WORDS)...

  20. C-Peptide Test

    Science.gov (United States)

    ... also be used in conjunction with insulin and glucose levels to help diagnose the cause of documented hypoglycemia and to monitor its treatment. Symptoms of hypoglycemia may be caused by excessive supplementation of insulin, alcohol consumption, inherited liver enzyme deficiencies, ...

  1. Somatostatin signaling system as an ancestral mechanism: Myoregulatory activity of an Allatostatin-C peptide in Hydra.

    Science.gov (United States)

    Alzugaray, María Eugenia; Hernández-Martínez, Salvador; Ronderos, Jorge Rafael

    2016-08-01

    The coordination of physiological processes requires precise communication between cells. Cellular interactions allow cells to be functionally related, facilitating the maintaining of homeostasis. Neuropeptides functioning as intercellular signals are widely distributed in Metazoa. It is assumed that neuropeptides were the first intercellular transmitters, appearing early during the evolution. In Cnidarians, neuropeptides are mainly involved in neurotransmission, acting directly or indirectly on epithelial muscle cells, and thereby controlling coordinated movements. Allatostatins are a group of chemically unrelated neuropeptides that were originally characterized based on their ability to inhibit juvenil hormone synthesis in insects. Allatostatin-C has pleiotropic functions, acting as myoregulator in several insects. In these studies, we analyzed the myoregulatory effect of Aedes aegypti Allatostatin-C in Hydra sp., a member of the phylum Cnidaria. Allatostatin-C peptide conjugated with Qdots revealed specifically distributed cell populations that respond to the peptide in different regions of hydroids. In vivo physiological assays using Allatostatin-C showed that the peptide induced changes in shape and length in tentacles, peduncle and gastrovascular cavity. The observed changes were dose and time dependent suggesting the physiological nature of the response. Furthermore, at highest doses, Allatostatin-C induced peristaltic movements of the gastrovascular cavity resembling those that occur during feeding. In silico search of putative Allatostatin-C receptors in Cnidaria showed that genomes predict the existence of proteins of the somatostatin/Allatostatin-C receptors family. Altogether, these results suggest that Allatostatin-C has myoregulatory activity in Hydra sp, playing a role in the control of coordinated movements during feeding, indicating that Allatostatin-C/Somatostatin based signaling might be an ancestral mechanism.

  2. Urinary C-peptide of insulin as a non-invasive marker of nutritional status: some practicalities.

    Directory of Open Access Journals (Sweden)

    James P Higham

    Full Text Available Nutritional status is a critical element of many aspects of animal ecology, but has proven difficult to measure non-invasively in studies of free-ranging animals. Urinary C-peptide of insulin (UCP, a small polypeptide cleaved in an equimolar ratio from proinsulin when the body converts it to insulin, offers great promise in this regard, and recent studies of several non-human primate species have utilized it with encouraging results. Despite this, there are a number of unresolved issues related to the collection, processing, storage and transport of samples. These include: contamination of samples on collection (most commonly by dirt or faeces, short-term storage before returning to a field station, differences in processing and long-term storage methods (blotting onto filter paper, freezing, lyophilizing, and for frozen samples, transportation while keeping samples frozen. Such issues have been investigated for urine samples in particular with respect to their effects on steroid hormone metabolites, but there has been little investigation of their effects on UCP measurement. We collected samples from captive macaques, and undertook a series of experiments where we systematically manipulated samples and tested the effects on subsequent UCP measurements. We show that contamination of urine samples by faeces led to a decrease in UCP levels by >90%, but that contamination with dirt did not have substantial effects. Short-term storage (up to 12 hours of samples on ice did not affect UCP levels significantly, but medium-term storage (up to 78 hours did. Freezing and lyophilization for long-term storage did not affect UCP levels, but blotting onto filter paper did. A transportation simulation showed that transporting frozen samples packed in ice and insulated should be acceptable, but only if it can be completed within a period of a few days and if freeze-thaw can be avoided. We use our data to make practical recommendations for fieldworkers.

  3. Somatostatin signaling system as an ancestral mechanism: Myoregulatory activity of an Allatostatin-C peptide in Hydra.

    Science.gov (United States)

    Alzugaray, María Eugenia; Hernández-Martínez, Salvador; Ronderos, Jorge Rafael

    2016-08-01

    The coordination of physiological processes requires precise communication between cells. Cellular interactions allow cells to be functionally related, facilitating the maintaining of homeostasis. Neuropeptides functioning as intercellular signals are widely distributed in Metazoa. It is assumed that neuropeptides were the first intercellular transmitters, appearing early during the evolution. In Cnidarians, neuropeptides are mainly involved in neurotransmission, acting directly or indirectly on epithelial muscle cells, and thereby controlling coordinated movements. Allatostatins are a group of chemically unrelated neuropeptides that were originally characterized based on their ability to inhibit juvenil hormone synthesis in insects. Allatostatin-C has pleiotropic functions, acting as myoregulator in several insects. In these studies, we analyzed the myoregulatory effect of Aedes aegypti Allatostatin-C in Hydra sp., a member of the phylum Cnidaria. Allatostatin-C peptide conjugated with Qdots revealed specifically distributed cell populations that respond to the peptide in different regions of hydroids. In vivo physiological assays using Allatostatin-C showed that the peptide induced changes in shape and length in tentacles, peduncle and gastrovascular cavity. The observed changes were dose and time dependent suggesting the physiological nature of the response. Furthermore, at highest doses, Allatostatin-C induced peristaltic movements of the gastrovascular cavity resembling those that occur during feeding. In silico search of putative Allatostatin-C receptors in Cnidaria showed that genomes predict the existence of proteins of the somatostatin/Allatostatin-C receptors family. Altogether, these results suggest that Allatostatin-C has myoregulatory activity in Hydra sp, playing a role in the control of coordinated movements during feeding, indicating that Allatostatin-C/Somatostatin based signaling might be an ancestral mechanism. PMID:27288244

  4. Structural basis for distinctive recognition of fibrinogen [gamma]C peptide by the platelet integrin [alpha][subscript IIb][beta]3

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Timothy A.; Zhu, Jianghai; Xiao, Tsan (Harvard-Med)

    2009-01-12

    Hemostasis and thrombosis (blood clotting) involve fibrinogen binding to integrin {alpha}{sub IIb}{beta}{sub 3} on platelets, resulting in platelet aggregation. {alpha}{sub v}{beta}{sub 3} binding fibrinogen via an Arg-Asp-Gly (RGD) motif in fibrinogen's {alpha} subunit. {alpha}{sub IIb}{beta}{sub 3} also binds to fibrinogen; however, it does so via an unstructured RGD-lacking C-terminal region of the {gamma} subunit ({gamma}C peptide). These distinct modes of fibrinogen binding enable {alpha}{sub IIb}{beta}{sub 3} and {alpha}{sub v}{beta}{sub 3} to function cooperatively in hemostasis. In this study, crystal structures reveal the integrin {alpha}{sub IIb}{beta}{sub 3}-{gamma}C peptide interface, and, for comparison, integrin {alpha}{sub IIb}{beta}{sub 3} bound to a lamprey {gamma}C primordial RGD motif. Compared with RGD, the GAKQAGDV motif in {gamma}C adopts a different backbone configuration and binds over a more extended region. The integrin metal ion-dependent adhesion site (MIDAS) Mg{sup 2+} ion binds the {gamma}C Asp side chain. The adjacent to MIDAS (ADMIDAS) Ca{sup 2+} ion binds the {gamma}C C terminus, revealing a contribution for ADMIDAS in ligand binding. Structural data from this natively disordered {gamma}C peptide enhances our understanding of the involvement of {gamma}C peptide and integrin {alpha}{sub IIb}{beta}{sub 3} in hemostasis and thrombosis.

  5. Metabolism and placental transfer of /sup 125/I-proinsulin and /sup 125/I-tyrosylated C-peptide in the pregnant rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Gruppuso, P.A.; Susa, J.B.; Sehgal, P.; Frank, B.; Schwartz, R.

    1987-10-01

    /sup 125/I-Proinsulin or /sup 125/I-tyrosylated-C-peptide (/sup 125/I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with /sup 125/I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with /sup 125/I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of /sup 125/I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of /sup 125/I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of /sup 125/I-tyr-CP. When /sup 125/I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of /sup 125/I-tyr-CP, probably owing to placental degradation.

  6. Metabolism and placental transfer of 125I-proinsulin and 125I-tyrosylated C-peptide in the pregnant rhesus monkey

    International Nuclear Information System (INIS)

    125I-Proinsulin or 125I-tyrosylated-C-peptide (125I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with 125I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with 125I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of 125I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of 125I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of 125I-tyr-CP. When 125I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of 125I-tyr-CP, probably owing to placental degradation

  7. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide

    OpenAIRE

    Boyhan, Diane; Daniell, Henry

    2010-01-01

    Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene...

  8. Dessert Formulation Using Sucralose and Dextrin Affects Favorably Postprandial Response to Glucose, Insulin, and C-Peptide in Type 2 Diabetic Patients

    OpenAIRE

    Argyri, Konstantina; Sotiropoulos, Alexios; Psarou, Eirini; Papazafiropoulou, Athanasia; Zampelas, Antonios; Kapsokefalou, Maria

    2013-01-01

    BACKGROUND: Dessert compositions may conform to diabetic diet when it contains low sugar or artificial sweetener to replace sugar. However, it is still questionable whether glycemic control in type 2 diabetes patients is improved by the use of diet-conforming dessert compositions. OBJECTIVE: To compare, in type 2 diabetes patients, the glycemic, insulin, and C-peptide responses to seven modified dessert compositions for diabetics (D-dessert) with the response to seven similar desserts of non-...

  9. Sensitive and specific time-resolved fluorescence immunoassay of rat C-peptide for measuring hormone secretory and storage capacity of β-cells in vivo and in vitro.

    Science.gov (United States)

    van Genderen, Farah T; Gorus, Frans K; Pipeleers, Daniel G; van Schravendijk, Christiaan F H

    2013-05-01

    The limitations of current rat C-peptide assays led us to develop a time-resolved fluorescence immunoassay for measurements in plasma, incubation media, and tissue/cell extracts. The assay uses 2 monoclonal antibodies, binding to different parts of the C-peptide molecule, and allowing, respectively, capture of the peptide and its detection by europium-labeled streptavidin. It is performed on 25-μL samples for a dynamic range from 66pM up to 3900pM C-peptide and displays over 95% recovery of added peptide in the range of 111pM to 2786pM. Its inter- and intra-assay coefficients of variations are, respectively, lower than 7.6% and 4.8%. Cross-reactivities by rat insulin and by human and porcine C-peptide are negligible, and cross-reactivity by mouse C-peptide is 6% ± 2%. The assay has been validated for in vivo and in vitro measurements of C-peptide release and cellular content. Release patterns were similar to those for insulin and occurred in equimolar concentrations for both peptides. The molar C-peptide contents in purified β-cells and isolated islets were similar to the corresponding insulin contents. This was also the case for pancreatic extracts containing protease inhibitors. PMID:23525244

  10. Short reaction of C-peptide, glucagon-like peptide-1, ghrelin and endomorphin-1 for different style diet in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi; WANG Xin; ZHANG Mei-fang; LI Yan-xiang; LI Ying; GU Ting; XIA Fang-zhen; YU Jiao; LU Ying-li

    2011-01-01

    Background Food composition and style is changing dramatically now,which causes inappropriate secretion of hormones from brain,gastrointestinal and endo-pancreas,may be related to unbalance of glucose in blood.The aim of this study was to explore the fast response of C-peptide,glucagon-like peptide-1 (GLP-1),ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.Methods The study enrolled 57 patients with type 2 diabetes (20 men and 37 women,mean age (67.05±8.26) years).Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect.C-peptide,GLP-1,ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.Results The delta (2h-0h) of C- peptide in meal A was significantly lower than that in meal B (P=0.0004).C-peptide,GLP-1,ghrelin and EM-1 were obviously higher before meal B than those before meal A (P <0.0001,<0.0001,=0.001,=0.0004 respectively).Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P=-0.0005,0.0079 respectively).Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (rA0h=0.7836,rB0h=0.9368,rAsh=0.7615,rB2h=0.9409,rA(2h_0h)=0.7531,rB(2h-0h)=0.9980,respectively,P <0.0001).Conclusion Western style meal (high fat and protein food) could make more response of C-peptide than eastern style meal,and could stimulate more gut hormones (GLP-1,ghrelin) and brain peptide (EM-1) at the first phase of digestion.

  11. Changes of Leptin Level in Serum, Cord Venous Blood and Placenta in Women with Gestational Diabetes Mellitus and Correlations with Insulin and C-Peptide

    Institute of Scientific and Technical Information of China (English)

    Jin-ming ZHU; Li SHI; Xiao-yuan LU; Rong-rong ZHANG; Min LI; Xiao-ning ZHANG

    2014-01-01

    ObjectiveTo investigate the changes of leptin levels in serum, cord venous blood and placenta and examine the possible relationships among them in women with gestational diabetes mellitus (GDM).Methods This case-control study was performed in 40 women with GDM and 40 normal women. The women with GDM received dietary advice, blood glucose monitoring and insulin treatment when necessary. Maternal serum and venous cord blood leptin, insulin and C-peptide levels were detected by ELISA. The expression level of leptin in placenta was measured by an immunohistochemical method. Results1. Leptin, insulin and C-peptide levels in serum of the women with GDM were significantly higher than those of the normal women (P<0.01,P<0.05, P<0.01). 2. Cord venous blood leptin and insulin in GDM group were significantly higher than in the normal group (P<0.01,P<0.05). No significant difference was found in cord venous blood C-peptide between two groups. 3. The expression of placenta leptin protein was significantly higher in GDM women than in normal women (P<0.01). There were positive correlations between placental leptin, cord venous leptin and insulin, birth weight, ponderal index in GDM women (r=0.37,P<0.05;r=0.39,P<0.05;r=0.53,P<0.01;r=0.54,P<0.01). However, there was no correlation between placental leptin and serum leptin.Conclusion The women with GDM and their fetuses suffer from hyperleptinaemia and hyperinsulinaemia. In the women with GDM, there was disorder in the interaction between leptin and insulin. The GDM women and their fetuses may be prone to insulin resistance and leptin resistance in late pregnancy.

  12. Analyses of the rate of decline in stimulated c-peptide 12 months after diagnosis in children with newly diag-nosed type 1 diabetes. results from the Hvidoere study group on childhood diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Porksen, S.; Nielsen, L.B.;

    2010-01-01

    Objectives: Direct measurement of C-peptide has been recommended to provide the most appropriate primary outcome in trials evaluating the efficacy of therapies to preserve beta-cell function. The aim of the present study was to quantitatively characterize the natural history of disease progression...... samples were centrally analyzed. The linearity of the slope of decline in stimulated C-peptide was analyzed from 3–12 months on a logarithmic scale. Linear mixed-effect models were used to determine cohort differences. Results: Maximum values of stimulated C-peptide were reached at a duration of three...... months. Thereafter there was a linear decline in stimulated C-peptide for all age groups above 5 years in both cohorts. The mean value for the disappearance rate in stimulated C-peptide was 7.2 ± 0.9%/month for the Hvidoere and 9.4 ± 0.8%/month for the Danish cohort (NS, P = 0.12). The combined slope...

  13. Research Progress on C-peptide and Atherosclerosis%C肽与动脉粥样硬化的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘谦

    2016-01-01

    以胰岛素抵抗为特征的代谢综合征及2型糖尿病患者倾向于更早期发生弥漫性动脉粥样硬化,甚至出现于高血糖之前,动脉粥样硬化是糖尿病死亡的首要原因.除了传统危险因素外,近年发现一直被认为无生物活性的C肽可能参与了动脉粥样硬化的关键发展步骤,其参与了炎症反应、促进单核巨噬细胞迁移趋化及向泡沫细胞转化、促进血管平滑肌细胞的增殖,几项队列研究提示血清C肽水平升高与全因死亡、心血管疾病、恶性肿瘤死亡相关.文章就C肽的生物学作用从基础研究到临床研究进展做一综述.%The patients with metabolic syndrome or type 2 diabetes mellitus are characterized by insulin resistance and have more risks to develop extensive atherosclerosis,even it occurs before hyperglycemia.Atherosclerosis is the leadng cause of death in diabetic population.Thus it is important to explore the mechanisms of atherosclerosis.Besides the traditional risk factors,C-peptide which is considered no biological activity may play role in atherogenesis.It involves inflammation of artery and results in monocyte/macrophage accumulation as well as smooth muscle cell proliferation.Several cohort studies suggest that increased C-peptide levels relate to all-cause death,cardiovascular disease and cancer mortality.This review focuses on the new biological functions of C-peptide based on in vitro,vivo research and clinical studies.

  14. Skim Milk, Whey, and Casein Increase Body Weight and Whey and Casein Increase the Plasma C-Peptide Concentration in Overweight Adolescents12

    DEFF Research Database (Denmark)

    Arnberg, Karina; Mølgaard, Christian; Michaelsen, Kim Fleischer;

    2012-01-01

    /L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered...... insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12–15 y with a BMI of 25.4 ± 2.3 kg/m2 (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein......In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma...

  15. Responses of plasma cyclic AMP, serum immunoreactive insulin, C-peptide immunoreactivity and blood sugar levels to glucagon in patients with liver diseases.

    Directory of Open Access Journals (Sweden)

    Shimamura,Junnosuke

    1985-10-01

    Full Text Available Levels of plasma cyclic AMP, serum immunoreactive insulin (IRI, serum c-peptide immunoreactivity (CPR and blood sugar (BS were determined 0, 15, 30, 45 and 60 min after a glucagon injection (0.01 mg per kg body weight in normal controls, patients with acute hepatitis and liver cirrhosis. Plasma cyclic AMP responses to glucagon in liver disease patients varied widely in peak value, and only in patients with fulminant hepatitis and decompensated liver cirrhosis with poor prognosis was the response suppressed. The peak response of BS was found significantly later in liver cirrhosis patients than in normal controls. IRI and CPR responses to glucagon were lower in acute hepatitis patients than in normal controls and liver cirrhosis patients. IRI levels and their sum were also lower in acute hepatitis patients, although CPR levels were not significantly different. Thus, the ratio of the sum of CPR from 0 to 60 min to that of IRI was significantly higher in acute hepatitis, indicating impaired pancreatic secretion of insulin to glucagon stimulation as well as increased uptake of insulin by the liver in acute hepatitis.

  16. Investigation of relationship between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitusF%探究血清C肽与2型糖尿病视网膜病变的关系

    Institute of Scientific and Technical Information of China (English)

    范进绵; 高俊泽

    2015-01-01

    目的:对血清C肽与2型糖尿病视网膜病变(DR)的关系进行分析与探讨。方法120例2型糖尿病患者,根据患者病情将其分为三组,即:无糖尿病视网膜病变(NDR)组40例,非增殖性糖尿病视网膜病变(NPDR)组42例,增殖性糖尿病视网膜病变(PDR)组38例。以电化学发光法对所有患者空腹血清C肽进行测定。结果三组患者空腹血清C肽水平均呈现下降趋势,三组比较,差异具有统计学意义(P<0.05)。血清C肽与2型糖尿病视网膜病变程度呈负相关。结论研究表明,在2型糖尿病视网膜病变中,血清C肽含量会由于病变程度的加深而逐渐降低,血清C肽水平是2型糖尿病视网膜病变进展的重要标志。%ObjectiveTo analyze and investigate the relationship between serum C-peptide and diabetic retinopathy (DR) in type 2 diabetes mellitus.MethodsA total of 120 type 2 diabetes mellitus patients were divided by their illness condition into three groups, as non diabetic retinopathy (NDR) group with 40 cases, non proliferative diabetic retinopathy (NPDR) group with 42 cases, and proliferative diabetic retinopathy (PDR) group with 38 cases. Electrochemiluminescence method was applied for detection of serum C-peptide in all patients.ResultsAll the three groups had decreased levels of fasting serum C-peptide, and the difference had statistical significance across the three groups (P<0.05). There was a negative correlation between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitus.ConclusionThis study shows the content of serum C-peptide will decrease along with the development of diabetic retinopathy in type 2 diabetes mellitus, therefore, serum C-peptide acts as an important indicator for progression of diabetic retinopathy in type 2 diabetes mellitus.

  17. 探究血清C肽与2型糖尿病视网膜病变的关系%Investigation of relationship between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitusF

    Institute of Scientific and Technical Information of China (English)

    范进绵; 高俊泽

    2015-01-01

    ObjectiveTo analyze and investigate the relationship between serum C-peptide and diabetic retinopathy (DR) in type 2 diabetes mellitus.MethodsA total of 120 type 2 diabetes mellitus patients were divided by their illness condition into three groups, as non diabetic retinopathy (NDR) group with 40 cases, non proliferative diabetic retinopathy (NPDR) group with 42 cases, and proliferative diabetic retinopathy (PDR) group with 38 cases. Electrochemiluminescence method was applied for detection of serum C-peptide in all patients.ResultsAll the three groups had decreased levels of fasting serum C-peptide, and the difference had statistical significance across the three groups (P<0.05). There was a negative correlation between serum C-peptide and diabetic retinopathy in type 2 diabetes mellitus.ConclusionThis study shows the content of serum C-peptide will decrease along with the development of diabetic retinopathy in type 2 diabetes mellitus, therefore, serum C-peptide acts as an important indicator for progression of diabetic retinopathy in type 2 diabetes mellitus.%目的:对血清C肽与2型糖尿病视网膜病变(DR)的关系进行分析与探讨。方法120例2型糖尿病患者,根据患者病情将其分为三组,即:无糖尿病视网膜病变(NDR)组40例,非增殖性糖尿病视网膜病变(NPDR)组42例,增殖性糖尿病视网膜病变(PDR)组38例。以电化学发光法对所有患者空腹血清C肽进行测定。结果三组患者空腹血清C肽水平均呈现下降趋势,三组比较,差异具有统计学意义(P<0.05)。血清C肽与2型糖尿病视网膜病变程度呈负相关。结论研究表明,在2型糖尿病视网膜病变中,血清C肽含量会由于病变程度的加深而逐渐降低,血清C肽水平是2型糖尿病视网膜病变进展的重要标志。

  18. 重组人源胰岛素原C肽在大肠杆菌中的克隆、表达与纯化%Cloning,expression and purification of recombinant human proinsulin C-peptide in E.coli

    Institute of Scientific and Technical Information of China (English)

    王学军; 顾凯; 曹荣月; 林洁; 吴洁; 刘景晶

    2006-01-01

    目的:构建一种新型表达载体(pEDCC),表达并纯化得到人源胰岛素原C肽.方法:将编码截短的门冬酰胺酶突变体(ansB-C),天然C肽,人IgG1铰链区(hinge),额外的酸敏感二肽(DP)以及富含碱性氨基酸的8肽(KRKRKKSR)的核苷酸序列依次分别插入pET28a载体中,构建表达载体pEDCC.在乳糖的诱导下,融合蛋白ansB-C-hinge-DPKRKRKKSRNGSGR-C-peptide以包涵体形式高效表达.融合蛋白经洗涤和乙醇分级沉淀纯化后,通过酸水解将PKRKRKKSRNGSGR-C-peptide释放出来.C肽N端14肽用胰蛋白酶切割,通过DE52柱与C-peptide分离.结果:构建的表达载体pEDCC序列正确,融合蛋白经分离纯化得到了高纯度的重组人源胰岛素原C肽.结论:以截短的门冬酰胺酶作为融合伙伴,并以富含碱性氨基酸的8肽调节等电点是一种生产重组人源胰岛素原C肽的有效方法.%Aim:To obtain recombinant human proinsulin C-peptide,a novel expression vector pEDCC was constructed to facilitate the expression and purification of C-peptide. Methods:Gene fragments encoding a truncated asparaginase fragment mutant,native C-peptide,a hinge fragment of human IgG1,an extra acid-labile dipeptide and a basic-amino-acid-riched octopeptide were introduced in turn into plasmid pET28a. The fusion protein ansB-C-hinge-DPKRKRKKSRNGSGR-C-peptide was expressed effectively as inclusion bodies after induced by lactose and partially purified by means of washing and ethanol fractionation. After being hydrolyzed,the polypeptide PKRKRKKSRNGSGR-C-peptide was liberated from the fusion partner. The N-terminal tetradecapeptide extension of C-peptide was subsequently cleaved by trypsin and removed by DE52 column. Results:The nucleotides sequence of plasmid pEDCC was confirmed to be identical with that of designed fusion protein. Recombinant human proinsulin C-peptide was obtained with high purity after purification. Conclusion:Employing truncated asparaginase as the fusion partner and basic

  19. Development of a time-resolved fluoroimmunoassay kit for detecting C-peptide%C-肽时间分辨荧光免疫分析试剂盒的研制

    Institute of Scientific and Technical Information of China (English)

    刘忠民; 张婷; 冯健明; 郑贵星

    2009-01-01

    目的 研制血清C-肽的时间分辨荧光免疫分析(TRFIA)试剂盒.方法 采用双抗体夹心法建立C-肽TRFIA试剂盒,并进行方法学评价.结果 C-肽可测量范围为0.4~20 ng/mL;分析敏感性为0.23 ng/mL;分析批内、批间精密度分别为7.99%、11.97%;C-肽回收率为99.57%;与胰岛素和胰岛素原无交叉反应.稳定性试验表明,试剂可以贮存在4 ℃稳定9个月,37 ℃稳定7 d;该试剂盒测试200份正常人血清样本,其参考范围为0.358~3.590 ng/mL;收集122份血清样本,用该试剂盒与国外其他方法的同类试剂盒同时检测,其相关系数为0.943 2,线性方程为Y=0.985 4X+0.506 3.结论 C-肽TRFIA试剂盒各项指标均达到临床检测要求,适合临床推广使用.%Objective To develop a time-resolved fluoroimmunoassay(TRFIA) kit for detection of C-peptide in serum. Methods Two anti-C-peptide monoclonal antibodies were used to develop the sandwich TRFIA kit for detection of C-peptide in serum and its methodology was evaluated. Results The detection range of C-peptide was 0.4-20 ng/mL.The analytical sensitivity was 0.23 ng/mL. The intra-assay and inter-assay coefficients of variation were 7.99% and 11.97% respectively. The recovery rate was 99.57%. There was no cross-reactivity with insulin and proinsulin. The TRFIA C-peptide reagents could be stored at 4 ℃ for 9 months and at 37 ℃ for 7 days. The reference value for TRFIA C-peptide kit in healthy subjects(200 cases) was 0.358-3.590 ng/mL. The correlation coefficient of blood samples detection results(122 cases) between this TRFIA kit and commercially available electrochemiluminescense immunoassay C-peptide kits was 0.943 2. The linear equation was Y=0.985 4X+0.506 3. Conclusions The developed TRFIA C-peptide kit is valuable for clinical application with good sensitivity, precision, accuracy, specificity and stability.

  20. Effect of C-peptide on the Migration and Proliferation of VSMCs%C肽在血管平滑肌细胞增生和迁移中的作用

    Institute of Scientific and Technical Information of China (English)

    余小平

    2012-01-01

    C肽是胰岛B细胞分泌的,是胰岛素原转化成胰岛素的副产物.长期以来,一直认为C肽无生物活性,在临床上一直作为判断B细胞功能的指标.随着近年来的研究进展,多项基础和临床研究都显示C肽水平与心血管、神经功能密切相关,从而日益受到重视.现从C肽对血管平滑肌细胞增生与迁移的作用以及可能的信号通路和相关基因等方面的研究进展进行综述.%C-peptide is secreted by pancreatic B cell and cleaved from the processing oi proinsulin to insulin. For decades, studies reported no biological junction oi C-peptide and it only served as an indicator oi pancreatic B cell junction in the clinical. But recently,a number oi basic and clinical investigators have revealed that the level oi C-peptide is closely related to the cardiovascular and neurological function, which is being paid increasing attention. Here is to make a review on the current research progress oi C-peptide effect on vascular' smooth muscle cells( VSMCs)migration and proliferation and possible signal pathways and the related genes.

  1. Application of Reaction Type of C-peptide Release Test in Diabetes Mellitus%C肽释放反应类型在糖尿病中的应用

    Institute of Scientific and Technical Information of China (English)

    陈栋; 段文若; 何娟; 卢振芳

    2001-01-01

    为探讨C肽(CP)释放试验及其反应曲线类型,在评价糖尿病(DM)患者胰岛β细胞功能、指导选择治疗方案等方面的作用,本文对67名正常人和217例DM患者行C肽释放试验测定,并对结果进行比较分析。结果表明,CP释放试验较好地反映胰岛β细胞功能状态,餐后CP峰值≥0.6nmol/L,它可作为DM患者是否使用口服降糖药物治疗的界限,但应结合分析CP释放反应类型以选择调整治疗方案。CP释放试验在评价胰岛β细胞功能、指导分型和选择治疗方案方面有非常重要的作用。%The article is to confirm the effect of C-peptide release test and types of release reaction in appraisal of pancreas function of β-cell and selection of treatment for diabetes mellitus (DM) patients.The serum C-peptide release test of 67 normal controls and 217 DM patients were determined by RIA,and the results were analyzed and compared.C-peptide release test can reflect the pancreas function of β-cell better,the peak of C-peptid≥0.6nmol/L after lunch can be the limit of whether to reduce the level of blood glucose only by oral drug.We should adjust the treatment through analyzing the type of C-peptide release reaction.C-peptide release test is very important in evaluating the pancreas function of β-cell,classifying the type of DM and selecting the treatement.

  2. The alteration and investigation of c-peptide, glycosylated hemoglobin and sensitive C-reactive protein test of gestational diabetes mellitus%妊娠糖尿病患者C-P、HbAlc和hs-CRP的改变及意义

    Institute of Scientific and Technical Information of China (English)

    谢则金; 王厚照; 黄璐; 黄幼芳

    2011-01-01

    目的 探讨C肽(C-P)、糖化血红蛋白(HbAlc)和超敏C反应蛋白(hs-CRP)在妊娠糖尿病诊断中的临床意义.方法 对正常对照组36例、正常妊娠组50例及妊娠糖尿病组56例采用生化和化学发光免疫方法进行hs-CRP、HbAlc、C-P的测定.结果 妊娠糖尿病组hs-CRP、HbAlc和C-P结果与正常妊娠组相比均明显增高(P<0.01);C-P对妊娠糖尿病诊断的特异性高于HbAlc(P<0.05);阳性预测值为91.42%,也明显高于HbAlc(P<0.05);两者联合检测的结果中,联合检测的特异性和阳性预测值分别为98.84%和96.77%,明显高于两者单独检测的结果(Pc -peptide, glycosylated hemoglobin and sensitive C -reactive protein test in diagnosis of gestational diabetes mellitns.Methods: 36 cases health control, 56 cases of gestational diabetes mellitus and 50 cases of normal pregnant women were selected.C - peptide, glycosylated hemoglobin and sensitive C - reactive protein test were measured by biochemical and chemiluminescence immunoassay methods.Results: Compared with the control and the normal pregnant group,the values of glycosylated hemoglobin, C - peptide and sensitive C - reactive protein were higher apparently in the gestational diabetes mellitus group ( P <0.01 ).The specificity of c -peptide were significantly higher than glycosylated hemoglobin in the gestational diabetes mellitus; The specificity and the positive (98.84%and 96.77% ) predictive value of combined detection of aglycosylated hemoglobin and c - peptide were significantly higher than Single detection ( P <0.05 ).Conclusions: There were high value of c - peptide, glycosylated hemoglobin and sensitive C -reactive protein test in diagnosis of gestational diabetes mellitus; Combined detection of C - peptide, glycosylated

  3. The effect of C-peptide on acute lung injury after hemorrhagic shock in rats%C 肽对失血性休克大鼠急性肺损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    张宇; 苏君梅; 陈维亚

    2014-01-01

    Objective To investigate the effect of C-peptide on acute lung injury after hemorrhagic shock in rats .Methods Male Wistar rats were randomly divided into 3 groups: sham, Ringer's lactate(RL) and C-peptide groups.The level of MPO in lung tissue was detemined.Plasma levels of IL-1, IL-6, TNF-αwere determined by ELISA method .The expression of NF-κB was detected by Western blot in lung tissue .Results The level of MPO in lung tissue , and Plasma levels of IL-1,IL-6, TNF-αincerased in C-peptide group and RL group compared with Sham group (P<0.01), The level of MPO in lung tissue,and Plasma levels of IL-1,IL-6, TNF-αincerased in C-peptide group decreased more significantly thanin RL group(P <0.01).The expression of NF-κB in lung tissure increased in C-peptide group and RL group comparedwith Sham group(P <0.01), The expression of NF-κB in C-peptide group decreased more significantly than in RL group(P <0.01).Conclusion C-peptide may exert renoprotective effects on acute lung injury after hemorrhagic shock byinhibiting inflammation.%目的:探讨C肽复苏对失血性休克大鼠急性肺损伤的保护作用。方法24只雄性Wistar大鼠随机分为3组:假手术组( Sham组),失血性休克+乳酸钠林格液复苏组( Ringer's lactate , RL组),失血性休克+C肽复苏组( C肽组)。实验结束测定各组大鼠肺组织髓过氧化物酶( marrow perioxidase ,MPO)活性;采用ELISA法检测各组大鼠血浆中炎症因子白细胞介素-1(interleukin 1, IL-1)、白细胞介素-6(interleukin 6, IL-6)及肿瘤坏死因子-α(tumor ne-crosisfactor, TNF-α)水平,Western blot法分析肺组织核转录因子-κB( nuclear factor-kappaB )蛋白表达水平,同时观察肺的组织学改变。结果与Sham组相比,C肽组和RL组肺组织MPO活性、血浆IL-1、IL-6、TNF-α水平显著升高(P<0.01),而C肽组较RL组则明显下降(P<0.01);C肽组与RL组肺组织NF-κB

  4. Effects of Clear Kefir on Biomolecular Aspects of Glycemic Status of Type 2 Diabetes Mellitus (T2DM Patients in Bandung, West Java [Study on Human Blood Glucose, c Peptide and Insulin

    Directory of Open Access Journals (Sweden)

    Judiono J

    2014-08-01

    Full Text Available Background: Diabetes Mellitus (DM triggers an excessive reaction of free-radicals. It increases reactive oxygen species and reduces antioxidants status as well as the β cell damage. Clear kefir was used for DM therapies, however it limited biomolecular exploration of its bioactive roles. Research aimed to investigate the effects of clear kefir on the biomolecular nature of the glycemic status of T2DM in Bandung. Methods: The randomized pretest-posttest control group was conducted by 106 T2DM patients. Research was done in several hospitals in Bandung and Cimahi, West Java from 2012–2013. Samples were divided randomly into three groups: (1 T2DM with HbA1c 7 fed standard diet and supplemented 200 ml/day by clear kefir, (3 T2DM with HbA1c was fed a standard diet as a control group. Dose response was obtained from a preeliminary vivo study, and then converted to human dosage by year 2011. Intervention was effectively done for 30 days. HbA1c was measured by HPLC. Fasting blood glucose (FBG and Postprandial blood glucose levels (PBG were measured by enzymes levels. C Peptide and insulin were measured by Elisa. Data was analyzed by a statictics programme by significance p<0,05. Study was approved by ethic committee. Results : HbA1c was significantly reduced in delta level (p<0.01 and FBG (p<0.015 among kefir groups. PBG was not significantly reduced among groups. C-Peptide was significantly increased in delta level, except in control group (p<0.014. Insulin was reduced significantly, except in control group (p<0.003. Conclusions : Supplementation of clear kefir reduced blood glucose levels (HbA1c, FBG, PBG and increased c-peptide. Clear kefir’s biomolecular mechanisms and chemistry characterization is a challenge for future studies.

  5. 2型糖尿病粗神经纤维损伤血清空腹C肽水平变化%Blood serum fasting C peptide, variation of large nerve fiber neuropathy

    Institute of Scientific and Technical Information of China (English)

    周怡昆; 张永红; 赵仁华; 张虹; 苏恒; 马杉; 薛元明

    2010-01-01

    Objective To study the blood serum fasting C peptide,variation of damaged large bers.Methods 1118 2 type diabetic patients were detected vibration perception,and sensation of cold,warmth,heatinduced pain,cold-induced pain by using vibration perception test method(VSA-3000)and quantitative analysis of detection of sensory disturbance TSA-2001,at the same time,to measure serum fasting C peptide.Results Serum fasting C peptide,mean level of damaged large ber group was(0.56 ± 0.49)nmol/l which was lower than that of damaged small fiber group(0.64 ± 0.58) nmol/l and that of normal sensation group(0.72 ± 0.49) nmol/L.P < 0.05.Conclusion lower serum fasting C peptide has relationship with large nerve fiber neuropathy.%目的 研究2型糖尿病粗细神经纤维损伤血清空腹C肽水平变化.方法 应用振动感觉分析仪及定量感觉障碍分析检测仪对1118例2型糖尿病患者行振动感觉,冷感觉,温感觉,冷痛觉,热痛觉检测,同时行空腹血清C肽水平检测.结果 粗神经纤维损伤的2型糖尿病患者空腹血清C肽水平为(0.56±0.49)nmol/L,明显低于细神经纤维损伤的空腹血清C肽水平(0.64±0.58)nmol/L和无感觉神经纤维损伤的空腹血清C肽水平(0.72±0.49)nmol/L,P<0.05.结论 低空腹C肽水平与粗有髓神经纤维损伤明显相关.

  6. Study on the relationship between changes of serum true insulin (Tl) C-peptide, GAD-Ab, INS-Ab contents and age, course of disease, degree of obesity in patients with DM2

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum TI, C-peptide, GAD-Ab and INS-Ab in different groups of patients with DM2 (age,course of disease and degree of obesity). Methods: Serum C-peptide(with CLIA), INS-Ab(with RIA) and TI, GAD-Ab(with ELISA) contents were measured in altogether 428 patients with DM2. Relationship between changes of the above parameters and different groups of patients was studide in accordance with age, course of disease and degree of obesity respectively. Results: 1)Relationship among different age groups:(below 50, n=86, 51-70, n=216, over 71 n=126). The serum levels of the 4 parameters were significantly higher in all age group than those in the controls(n=40). Among the various age groups, the levels of all parameters were significantly lower in age group below 50 than the levels,in the other 2 groups with the only exception of INS-Ab, which was not significantly different from that in age group 51-70.The levels were significantly different between age-group 51-70 and age groups over 70, with the only exception of GAD-Ab, which was about the same in the two age-groups. 2)Relationship between changes of serum levels and course of disease(below 5yrs n=157, 6-10yrs n=168,over 1yrs,n=103). The serum levels in patients with disease less than 5years were significantly lower than those in other groups with the exception of GAD-Ab, which was not significantly different from that in patients with disease 6-10 years. 3) Relationship among different degree of obesity(non-obese, BMIBMI≥25, n=202, super-obese BMI≥32 n=50): The serum levels of all the parameters were significantly lower in the non-obese subjects than those in the other two groups.The levels in the super-obese group were also significantly higher than those in the obese group (P<0.01, P<0.05). Conclusion: Serum levels of the 4 parameters (TI, C-peptide, GAD-Ab, INS-Ab)were significantly increased in patients with DM2, especially in the older patients with prolonged course of disease as

  7. Serum C peptide and glycosylated hemoglobin the significance of combined detection of diabetes diagnosis%血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义

    Institute of Scientific and Technical Information of China (English)

    闫东; 王霞

    2015-01-01

    目的:总结血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义,重点研究能够提升糖尿病病人诊断效率的重要方案。方法该研究资料选取2013年11月-2014年11月期间在我院接受诊治的糖尿病病人45例,视作实验组。同期选取45名来院体检的健康者为对照组,均予以血清C肽与糖化血红蛋白联合检测,同时对两组研究对象糖化血红蛋白、餐后两小时血糖值、空腹血糖值等指标进行对比。结果研究结果发现,对照组病患血清C肽值是(1.42±0.41)μg/l,实验组是(1.02±0.08)μg/l;实验组糖化血红蛋白是(10.05±2.19)%,对照组是(5.08±0.41)%;实验组空腹血糖值是(8.91±2.62)mmol/l,对照组是(4.19±0.62)mmol/l;实验组餐后两小时血糖值是(12.05±2.04)mmol/l,对照组是(4.79±1.52)mmol/l,两组研究对象在糖化血红蛋白、餐后两小时血糖值、空腹血糖值等指标方面的对比差异十分显著(P<0.05)。结论血清C肽与糖化血红蛋白联合检测对糖尿病诊断的意义十分突出,这是由于糖尿病病人血清C肽与糖化血红蛋白均会出现异常,因此检测结果可用作判断机体疾病严重性的重要指标。%Objective to summarize the serum C peptide and glycosylated hemoglobin significance of combined detection of diabetes diagnosis, key research important scheme can improve diabetes patients diagnosis efficiency.Methods this study data selection in November 2013 - November 2014 to accept the diagnosis and treatment in our hospital during the period of 45 cases of diabetes patients, as the experimental group. Selection in the same period of 45 to hospital medical healthy subjects as control group, both to serum C peptide and glycated hemoglobin joint detection, at the same time on two groups of research object glycosylated hemoglobin, two hours after the meal, fasting blood sugar levels in blood sugar levels such as index were compared.Results the results of the study

  8. Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.

    Science.gov (United States)

    Ido, Yasuo

    2016-07-01

    Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C-peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3. PMID:27181414

  9. Intrapulmonary administration of natural honey solution, hyperosmolar dextrose or hypoosmolar distill water to normal individuals and to patients with type-2 diabetes mellitus or hypertension: their effects on blood glucose level, plasma insulin and C-peptide, blood pressure and peaked expiratory flow rate.

    Science.gov (United States)

    Al-Waili, N

    2003-07-31

    Safety and effect intrapulmonary administration (by inhalation) of 60 % honey solution, 10% dextrose or distill water on blood sugar, plasma insulin and C-peptide, blood pressure, heart rate, and peaked expiratory flow rate (PEFR) in normal or diabetic subjects were studied. - Twenty-four healthy subjects, 16 patients with type 11 diabetes mellitus and six patients with hypertension were entered for study. They were underwent complete physical examination and laboratory investigations. Twelve healthy subjects were subjected for distill water inhalation for 10 min, and after one week they received inhalation of honey solution (60% wt/v) for 10 min. Another 12 healthy subjects received inhalation of 10% dextrose for 10 min. Blood glucose level, plasma insulin and C-peptide, blood pressure, heart rate and PEFR were estimated before inhalation and during 2-3 hrs after inhalation, at 30 min intervals. Random blood glucose level was estimated in eight patients with poorly controlled diabetes mellitus, and repeated 30 min after honey inhalation. One week later, fasting blood glucose level was estimated in each patient and blood glucose level was re-estimated during three hrs after honey inhalation, at 30 min intervals. Glucose tolerance test was performed in another eight patients with type-2 diabetes mellitus, and after one week the procedure was repeated with inhalation of honey, which was started immediately after ingestion of glucose. Six hypertensive patients received honey inhalation for 10 min; supine blood pressure and heart rate were measured before and after inhalation. - Results showed that in normal subjects distill water caused mild elevation of blood glucose level, mild lowering of plasma insulin, and significant reduction of plasma C-peptide. 10% dextrose inhalation caused mild reduction of plasma insulin and C-peptide and unremarkable changes in blood glucose level. No significant changes were obtained in blood pressure, heart rate or PEFR after distill

  10. 血浆C肽水平变化早期预测2型糖尿病并发周围感觉神经病变的价值%The value of plasma C-peptide levels in early prediction of type 2 diabetes mellitus with peripheral sensory neuropathy

    Institute of Scientific and Technical Information of China (English)

    邓彦; 刘阳优; 梁芬; 陈彩秀; 李润生; 彭文宏

    2014-01-01

    目的 探讨血浆C肽水平变化早期预测2型糖尿病并发周围感觉神经病变的价值.方法 500例2型糖尿病予以震动觉、痛觉、温度觉、触压觉、踝反射检测,根据周围感觉神经检测结果分为四组:正常组(159例)、轻度异常组(120例)、中度异常组(121例)、重度异常组(100例).同时测定其空腹和餐后2h血浆C肽,并与周围感觉神经变化进行分析.制作受试者工作特征(ROC)曲线,找出诊断糖尿病周围感觉神经病变的最佳临界点.结果 四组空腹血浆C肽比较差异无统计学意义(F=1.632,P> 0.05).餐后2h血浆C肽从正常组到轻度异常组再到中度异常组逐渐增高[(1.110±0.526)、(1.324±0.490)、(1.573±0.716) μg/L],而到重度异常组[(0.910±0.465)μg/L]明显下降且低于正常组,差异均有统计学意义(P<0.05).当餐后2h血浆C肽为1.173 μg/L时,得到最大约登指数0.366.结论 糖尿病并发周围感觉神经病变的早期可能与空腹C肽水平变化关系不大,而与餐后2h血浆C肽水平变化有关.动态观察餐后2h血浆C肽水平变化可能有助于早期发现糖尿病周围感觉神经病变.%Objective To explore the value of plasma C-peptide levels in early prediction of type 2 diabetes mellitus with peripheral sensory neuropathy.Methods The vibration perception threshold,pain,temperature sensation,touch-pressure sensation,ankle reflex was detected in 500 eases of type 2 diabetes mellitus,and the patients were divided into 4 groups according to peripheral sensory nerve test results:normal group (159 cases),mildly abnormal group (120 cases),moderately abnormal group (121 cases) and severely abnormal group (100 cases).Fasting and 2-hour postprandial C-peptide levels were determined and analysed with peripheral sensory nerve changes.The receiver-operating characteristic (ROC) curve was used to find the best critical point for diagnosis of diabetic peripheral sensory neuropathy.Results The fasting C-peptide

  11. 2型糖尿病合并骨质疏松症患者血清C肽、骨钙素水平检测%Expression of proinsulin C-peptide and bone Gla protein in patients with type 2 diabetes mellitus complicated with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    古丽努尔·伊斯拉木; 李应琴

    2014-01-01

    目的:检测2型糖尿病合并骨质疏松症患者血清C肽及骨钙素( BGP )水平。方法:收集2013年2月至2014年1月本院老年病科住院治疗的2型糖尿病患者96例,按骨质疏松症诊断标准分为2型糖尿病合并骨质疏松症组( A组)和单纯2型糖尿病组( B组)。测定两组患者大转子、股骨颈、Wards区的骨密度,比较两组患者的血清甘油三酯( TG)、空腹血糖( FBG)、总胆固醇( TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、餐后2 h血糖(P2hBG)、空腹C肽、餐后2 h C肽及BGP水平。结果:两组患者血清TG、FBG等生化指标差异均无统计学意义(均P>0.05)。 A组患者大转子、股骨颈及Wards区骨密度均显著低于B组(均P0.05). Bone densities of greater trochanter, femoral neck and Wards area of the observation group were significantly lower than those of the control group (P<0.05). Fasting Proinsulin C-peptide, postprandial 2 h Proinsulin C-peptide and BGP were significantly lower than those of the control group ( P<0.05) . Conclusion:Serum proinsulin C-peptide and BGP can be used as potential index for the screening on patients with type 2 diabetes complicated with osteoporosis.

  12. Effect of C-peptide on advanced glycation end products-induced oxidative stress in rat mesangial cells%C肽对晚期糖基化终末产物诱导的大鼠肾小球系膜细胞氧化应激的影响

    Institute of Scientific and Technical Information of China (English)

    许世清; 张文健; 刘虹麟; 娄晋宁; 王在; 彭亮; 房青; 游嘉; 邓婷婷; 郭彬

    2015-01-01

    Objective To investigate the effect of C-peptide on advanced glycation end products (AGE)-induced oxidative stress in rat mesangial cells and its mechanism. Methods Rat mesangial cells were cultured in the normal medium(Control group),or medium with 200 mg/L AGEs(AGEs group),or medium with 200 mg/L AGEs and 5μmol/L C-peptide(AGEs+C-peptide group)or medium with 10μmol/L H89(added in advance,and incubated for 30 min)and 200 mg/L AGEs and 5μmol/L C-peptide(AGEs+C-peptide+H89 group). The intracellular reactive oxygen species(ROS)was detected with fluorescence method,and the supernatant nitric oxide(NO)level was detected by Griess reaction. Real-time PCR and Western blotting were used to detect the expression of the receptor for advanced glycation endproducts (RAGE),protein kinase A(PKA),nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)and inducible nitric oxide synthase(iNOS). Non-parametric Kruskal-Wallis H test and Mann-Whitney U test were used to compare data between groups,and two groups,respectively. Results Compared with control group,the level of ROS and NO increased in AGEs group(193.7±6.4 vs 136.1±4.9;and 27.2±4.7 vs 15.5± 0.7,respectively,all U=0,P<0.05). C-peptide could suppress the production of ROS and NO. In AGEs+C-peptide group,ROS and NO reduced than AGEs group(136.9±14.3 vs 193.7±6.4 and 16.0±2.1 vs 27.2±4.7 respectively,all U=0,P<0.05). Compared with control group,AGEs could up-regulate the expression of RAGE(0.565±0.027 vs 0.148±0.006,U=0,P<0.05)but down-regulate PKA(0.085±0.035 vs 0.518±0.019, U=0,P<0.05). And AGEs increased the expression of NOX4 and iNOS(0.912±0.055 vs 0.105±0.012,and 0.279±0.003 vs 0.126±0.004 respectively,all U=0,P<0.05). Compared with AGEs group,C-peptide down-regulated RAGE(0.159 ± 0.003 vs 0.565 ± 0.027,U=0,P<0.05),up-regulated PKA(0.594 ± 0.079 vs 0.085 ± 0.035,U=0,P<0.05),and down-regulated NOX4 and iNOS(0.085±0.005 vs 0.912±0.055,and 0.071±0.016 vs 0.279 ± 0.003 respectively,all U=0,P<0

  13. 血清C肽与糖化血红蛋白联合检测在2型糖尿病诊断中的临床价值%Serum C Peptide and Glycosylated Hemoglobin Examination in the Diagno-sis of Type 2 Diabetes Clinical Value

    Institute of Scientific and Technical Information of China (English)

    王荔; 林飞

    2015-01-01

    目的:探讨血清C 肽与糖化血红蛋白联合检测在2型糖尿病诊断中的临床价值。方法选取该院2013年7月-2014年7月来就诊55例2型糖尿病患者,将其分观察组,并选取同时期正常健康体检者28名为对照组,对其分别进行糖化血红蛋白(HbAlc)、空腹血糖(FBG)、餐后2 h血糖及血清C肽指标进行检测,并对其进行比对。结果观察组糖化血红蛋白(HbAlc)(9.54±1.07)(%)、空腹血糖(FBG)(10.02±2.04)mmol/L、餐后2 h血糖(15.97±1.16)mmol/L、血清C肽(0.87±0.16)μg/L;对照组糖化血红蛋白(HbAlc)(5.28±0.84)%、空腹血糖(FBG)(4.35±0.38)mmol/L、餐后2h血糖(5.59±1.25)mmol/L、血清C肽(1.39±0.22)μg/L。从统计的数据上看,观察组空腹血糖(FBG)、糖化血红蛋白(HbAlc)及餐后2 h血糖明显高于对照组,两组比较差异具有统计学意义(t=18.36、t=14.54、t=37.55、P<0.01);而观察血清C肽指标明显低于对照组,两组比较差异具有统计学意义(t=12.29、P<0.01)。结论通过对血清C肽和糖化血红蛋白联合进行检测,可以对患者胰岛素分泌情况及病情严重程度做出准确的判断,为临床治疗方案提供可靠科学依据。%Objective To study the serum C peptide and glycosylated hemoglobin examination in the diagnosis of type 2 dia-betes clinical value.Methods Selection our hospital in July 2013 to July 2014 to 55 cases of patients with type 2 diabetes treatment,the observation group, and at the same time normal healthy check-up 28 cases as control group, the respectively are glycosylated hemoglobin (HbAlc), fasting blood glucose (FBG), 2 h postprandial blood glucose and serum c-peptide indi-cators for testing, and carries on the comparison. Results The observation group of glycosylated hemoglobin (HbAlc)(9.54±1.07)(%), fasting blood glucose (FBG)(10.02±2.04)mmol/L , 2 h postprandial blood glucose(15.97±1.16)mmol/L, serum C peptide (0.87±0.16)μg/L;Glycosylated hemoglobin (Hb

  14. Influence of Military Training on Interleukin 6, Interleukin 10, Insulin and C-peptide in Serum of Overweighted Recruits%军事训练对体质量超标新兵血清IL-6、IL-10和胰岛素、C肽的影响

    Institute of Scientific and Technical Information of China (English)

    罗显荣; 罗春生; 张红梅; 骆丽敏

    2013-01-01

    Objective To investigate the influence of military training on interleukin 6 (IL-6) , ingterleukin 10 (IL-10), insulin and C-peptide in overweighted recruits and supply reference for scientific training. Methods A total of 29 recruits in a land force were randomly selected and divided into normal weight group with body mass index (BMIX24 (20 cases) and overweight group (BMI≥24, 9 cases). Their blood samples before and eight weeks after training were collected. IL-6, IL-10, insulin and C-peptide were detected. Results The levels of IL-6, IL-10, insulin and C-peptide in the serum of the two groups had no difference before training (P>0. 05). IL-6 levels were significantly increased in the two groups after training (P<0. 05). The insulin level was increased after training in overweight group (P<0. 05). The IL-6 level in overweight group after training was significantly higher than that in normal weight group (P<0.01). Conclusion The increased exudationof insulin in overweighted recruits increased after military training may relate with the inflammatory response caused by IL-6.%目的 探讨军事训练对超重新兵血清白细胞介素6(interleukin 6,IL-6)、白细胞介素10(interleukin 10,IL-10)、胰岛素、C肽的影响及机制,为科学施训提供依据.方法 随机抽取某部新兵29人,根据体质量指数(body mass index,BMI)将新兵分为正常体质量组(BMI<24,20人)、超重组(BMI≥24,9人).训练前及训练8周后测试血清IL-6、IL-10、胰岛素、C肽水平.结果 两组新兵训练前血清IL-6、IL-10、胰岛素、C肽水平无明显差异(P>0.05);训练后两组IL-6水平均明显升高(P<0.05);超重组胰岛素水平明显升高(P<0.05).训练后超重组血清IL-6水平明显高于正常体质量组(P<0.01).结论 超重新兵军事训练后胰岛素分泌增加,可能与IL-6介导炎症反应有关.

  15. C-peptide levels predict type 2 diabetes remission after bariatric surgery.

    Science.gov (United States)

    Ramos-Leví, Ana M; Matía, Pilar; Cabrerizo, Lucio; Barabash, Ana; Torrejón, María José; Sánchez-Pernaute, Andrés; Torres, Antonio J; Rubio, Miguel A

    2013-01-01

    Introducción: La determinación del péptido C (pC) suele emplearse como un indicador de la reserva betapancreática. El objetivo de este estudio es evaluar si el pC basal, es un parámetro predictor de remisión de diabetes mellitus tipo 2 (DM2) tras cirugía bariátrica (CB). Material y métodos: Estudio retrospectivo de 22 pacientes con DM2 e IMC > 35 kg/m2, intervenidos mediante CB. Recogida de datos clínicos, antropométricos y analíticos relativos al metabolismo de la glucosa, antes de la CB y al año. Análisis de pacientes en remisión completa de DM2 al año de la CB (glucosa basal [GB] 3,75 ng/ml supuso una sensibilidad y especificidad para remisión de DM2 de 75% y 80%, respectivamente. La tasa de remisión de DM2 fue de 27,3% si el pC basal pre-CB 3,8 ng/ml (p = 0,010). Conclusiones: Los pacientes con pC basal preoperatorio elevado son los que mayores tasas de remisión alcanzan al año de la CB. Una concentración de pC basal > 3,75 ng/dL parece un buen predictor de remisión completa de DM2 al año de la CB.

  16. Cloning, expression, and purification of a recombinant Tat-HA-NR2B9c peptide.

    Science.gov (United States)

    Zhou, Hai-Hui; Zhang, Ai-Xia; Zhang, Yu; Zhu, Dong-Ya

    2012-10-01

    To design a peptide disrupting the interaction between N-methyl-d-aspartate receptors-2B (NR2B) and postsynaptic density protein-95 (PSD-95), a gene fragment encoding a chimeric peptide was constructed using polymerase chain reaction and ligated into a novel expression vector for recombinant expression in a T7 RNA polymerase-based expression system. The chimeric peptide contained a fragment of the cell membrane transduction domain of the human immunodeficiency virus type1 (HIV-1) Tat, a influenza virus hemagglutinin (HA) epitope-tag, and the C-terminal 9 amino acids of NR2B (NR2B9c). We named the chimeric peptide Tat-HA-NR2B9c. The expression plasmid contained a gene fragment encoding the Tat-HA-NR2B9c was ligated to the C-terminal fragment of l-asparaginase (AnsB-C) via a unique acid labile Asp-Pro linker. The recombinant fusion protein was expressed in inclusion body in Escherichia coli under isopropyl β-d-1-thiogalactopyranoside (IPTG) and purified by washing with 2M urea, solubilizing in 4M urea, and then ethanol precipitation. The target chimeric peptide Tat-HA-NR2B9c was released from the fusion partner following acid hydrolysis and purified by isoelectric point precipitation and ultrafiltration. SDS-PAGE analysis and MALDI-TOF-MS analysis showed that the purified Tat-HA-NR2B9c was highly homogeneous. Furthermore, we investigated the effects of Tat-HA-NR2B9c on ischemia-induced cerebral injury in the rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and found that the peptide reduced infarct size and improved neurological functions. PMID:22944204

  17. Determinants of C-peptide levels and acute insulin resistance/sensitivity in nondiabetic STEMI role of Killip class

    Directory of Open Access Journals (Sweden)

    Chiara Lazzeri

    2014-03-01

    According to our data, the development of acute insulin resistance in the early phase of STEMI can be viewed as an adaptive mechanism to stress (represented by acute myocardial ischemia, similar to other acute critical conditions, related to the severity of stress (that is to the hemodynamic impairment.

  18. Improvement of C peptide zero BMI 24-34 diabetic patients after tailored one anastomosis gastric bypass (BAGUA).

    Science.gov (United States)

    Garciacaballero, M; Martínez-Moreno, J M; Toval, J A; Miralles, F; Mínguez, A; Osorio, D; Mata, J M; Reyes-Ortiz, A

    2013-03-01

    Introducción: Aunque la cirugía bariátrica ha demostrado ser un método muy eficaz en el tratamiento de pacientes diabéticos cuyo páncreas aún es capaz de producir insulina (diabetes tipo 2), así como del síndrome metabólico y las complicaciones relacionadas con la diabetes, no hay información sobre el efecto de este tipo de cirugía en pacientes IMC 24-34 cuando el páncreas no produce insulina en absoluto (tipo 1, tipo LADA y diabetes tipo 2 de larga evolución, entre otros). Métodos: Presentamos datos preliminares de una serie de 11 pacientes todos con valores de Péptido C insulina, tanto de insulina rápida (de 40,6 ± 12,8 a 0 U/día) como de insulina retardada (41,27 ± 7,3 U/día a 15,2 ± 3,3 U/día). Se resolvieron el 100% de las comorbilidades estudiadas y se mejoraron algunas complicaciones graves derivadas de la diabetes como retinopatía o nefropatía. Conclusiones: El bypass gástrico de una anastomosis adaptado a pacientes diabéticos IMC24-34 con péptido C cero elimina el uso de insulina de acción rápida, reduce a una sola inyección diaria la insulina retardada y mejora el control glucémico. Tras la cirugía desaparecen el síndrome metabólico y los episodios severos de hipoglucemia, y mejora significativamente la retinopatía, neuropatía, nefropatía, vasculopatía periférica y cardiopatía.

  19. 胰岛素原C肽作用机制%Mechanism of Proinsulin C-peptide Action

    Institute of Scientific and Technical Information of China (English)

    刘智慧; 崔大敷

    2001-01-01

    @@ C肽是胰岛素原中连接AB两条链的连接肽。在胰岛β细胞分泌颗粒中,胰岛素原经蛋白酶裂解,形成等摩尔由AB链组成的胰岛素和C肽,然后分泌并进入血液。C肽的种族差异很大,其中人C肽含31个氨基酸。

  20. Synthetic lung surfactants containing SP-B and SP-C peptides plus novel phospholipase-resistant lipids or glycerophospholipids

    Science.gov (United States)

    Notter, Robert H.; Gupta, Rohun; Schwan, Adrian L.; Wang, Zhengdong; Shkoor, Mohanad Gh

    2016-01-01

    Background This study examines the biophysical and preclinical pulmonary activity of synthetic lung surfactants containing novel phospholipase-resistant phosphonolipids or synthetic glycerophospholipids combined with Super Mini-B (S-MB) DATK and/or SP-Css ion-lock 1 peptides that replicate the functional biophysics of surfactant proteins (SP)-B and SP-C. Phospholipase-resistant phosphonolipids used in synthetic surfactants are DEPN-8 and PG-1, molecular analogs of dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl-oleoyl phosphatidylglycerol (POPG), while glycerophospholipids used are active lipid components of native surfactant (DPPC:POPC:POPG 5:3:2 by weight). The objective of the work is to test whether these novel lipid/peptide synthetic surfactants have favorable preclinical activity (biophysical, pulmonary) for therapeutic use in reversing surfactant deficiency or dysfunction in lung disease or injury. Methods Surface activity of synthetic lipid/peptide surfactants was assessed in vitro at 37 °C by measuring adsorption in a stirred subphase apparatus and dynamic surface tension lowering in pulsating and captive bubble surfactometers. Shear viscosity was measured as a function of shear rate on a Wells-Brookfield micro-viscometer. In vivo pulmonary activity was determined by measuring lung function (arterial oxygenation, dynamic lung compliance) in ventilated rats and rabbits with surfactant deficiency/dysfunction induced by saline lavage to lower arterial PO2 to C. However, dual-peptide surfactants containing 1.5% S-MB DATK + 1.5% SP-Css ion-lock 1 combined with 9:1 DEPN-8:PG-1 or 5:3:2 DPPC:POPC:POPG had the greatest in vivo activity in improving arterial oxygenation and dynamic lung compliance in ventilated animals with ARDS. Saline dispersions of these dual-peptide synthetic surfactants were also found to have shear viscosities comparable to or below those of current animal-derived surfactant drugs, supporting their potential ease of deliverability by instillation in future clinical applications. Discussion Our findings support the potential of dual-peptide synthetic lipid/peptide surfactants containing S-MB DATK + SP-Css ion-lock 1 for treating diseases of surfactant deficiency or dysfunction. Moreover, phospholipase-resistant dual-peptide surfactants containing DEPN-8/PG-1 may have particular applications in treating direct forms of ARDS where endogenous phospholipases are present in the lungs.

  1. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    NARCIS (Netherlands)

    Pfleger, C; Kaas, A; Hansen, L; Alizadeh, B; Hougaard, P; Holl, R; Kolb, H; Roep, B O; Mortensen, H B; Schloot, N C

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated longi

  2. Association between age, IL-10, IFN gamma, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

    NARCIS (Netherlands)

    Kaas, A.; Pfleger, C.; Kharagjitsingh, A. V.; Schloot, N. C.; Hansen, L.; Buschard, K.; Koeleman, B. P. C.; Roep, B. O.; Mortensen, H. B.; Alizadeh, B. Z.

    2012-01-01

    AIMS: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. METHODS: Two hundred and twenty-seven patients from the Hvidoere Study Group were classif

  3. Association between age, IL-10, IFN gamma, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

    NARCIS (Netherlands)

    Kaas, A.; Pfleger, C.; Kharagjitsingh, A. V.; Schloot, N. C.; Hansen, L.; Buschard, K.; Koeleman, B. P. C.; Roep, B. O.; Mortensen, H. B.; Alizadeh, B. Z.

    2012-01-01

    Diabet. Med. 29, 734741 (2012) Abstract Aims The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFN?) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Methods Two hundred and twenty-seven patients from

  4. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C; Kaas, A; Hansen, L;

    2008-01-01

    longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated...

  5. Different short-term effect of protein and carbohydrate intake on TSH, growth hormone (GH), insulin, C-peptide, and glucagon in humans

    DEFF Research Database (Denmark)

    Matzen, L E; Andersen, B B; Jensen, B G;

    1990-01-01

    hormone (GH) and thyroid stimulating hormone (TSH) to protein and carbohydrate was identical, with a reduction in both GH and TSH, and nadir occurring after 45-60 min and 120 min, respectively. During the next 120 min TSH returned to starting level after carbohydrate intake but was still reduced after...... protein intake (p less than 0.04). After both diets GH increased after the initial decline, the increase was greatest after protein intake and maximum was reached at 180 min (p less than 0.02). It has been reported that the 5'-deiodination of T4 is stimulated by insulin and inhibited by glucagon......The effect of isocaloric (500 kcal) protein and carbohydrate ingestion was studied in a crossover study in nine healthy humans. Subjects were studied twice after overnight fasting, with an interval of 3 to 7 days. Blood was collected for 240 min after food ingestion. The initial reaction of growth...

  6. 胰岛素、胰岛素原、胰岛素类似物和C肽%Insulin,proinsulin,insulin - like substance and C - peptide

    Institute of Scientific and Technical Information of China (English)

    陆菊明

    2004-01-01

    人类认识到糖尿病(DM)的现象已有数千年历史。然而由于科学技术和知识水平的限制,直到1921年才由加拿大学者Bantng和Best从狗的胰腺中提取出胰岛素,从此开辟了DM治疗的新时代。胰岛素制剂的开发和临床应用经历了许多具有历史意义的过程。最早使用的胰岛素是动物胰腺组织的粗提物,以后经过不断纯化,衍生了许多胰岛素的制剂,广泛地应用于临床,在此基础上,近年又开发了胰岛素类似物(insulin analogue),制备成超短效和超长效胰岛素制剂,为临床应用提供了更好的选择。

  7. An Improved Solid Phase Synthesis of Human Proinsulin C-peptide%人胰岛素原C肽固相合成的改进

    Institute of Scientific and Technical Information of China (English)

    石嘉豪; 李江; 鞠彩娥; 崔大敷

    2003-01-01

    利用谷氨酸的γ羧基与4-甲基二苯甲基胺(MBHA)树脂的氨基偶联固相, 合成经HF切割去保护基后形成C端是谷氨酰胺的人胰岛素原C肽. MBHA树脂相对价格便宜, 此方法是制备人胰岛素原C肽的另一种尝试. 同时, 也用PAM树脂合成了人胰岛素原C肽类似物.

  8. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Kaas, A.; Hansen, L.;

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated...... longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated...... of CCR5 by therapeutic agents such as maraviroc may provide a new therapeutic target to ameliorate disease progression in type 1 diabetes. (C) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/7...

  9. Association between age, IL-10, IFN¿, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

    DEFF Research Database (Denmark)

    Kaas, A; Pfleger, Claudia Christina; Kharagjitsingh, A V;

    2012-01-01

    Aims: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFN¿) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Methods: Two hundred and twenty-seven patients from the Hvidoere Study Group were clas...

  10. Crucial elements that maintain the interactions between the regulatory TnaC peptide and the ribosome exit tunnel responsible for Trp inhibition of ribosome function.

    Science.gov (United States)

    Martínez, Allyson K; Shirole, Nitin H; Murakami, Shino; Benedik, Michael J; Sachs, Matthew S; Cruz-Vera, Luis R

    2012-03-01

    Translation of the TnaC nascent peptide inhibits ribosomal activity in the presence of l-tryptophan, inducing expression of the tnaCAB operon in Escherichia coli. Using chemical methylation, this work reveals how interactions between TnaC and the ribosome are affected by mutations in both molecules. The presence of the TnaC-tRNA(Pro) peptidyl-tRNA within the ribosome protects the 23S rRNA nucleotide U2609 against chemical methylation. Such protection was not observed in mutant ribosomes containing changes in 23S rRNA nucleotides of the A748-A752 region. Nucleotides A752 and U2609 establish a base-pair interaction. Most replacements of either A752 or U2609 affected Trp induction of a TnaC-regulated LacZ reporter. However, the single change A752G, or the dual replacements A752G and U2609C, maintained Trp induction. Replacements at the conserved TnaC residues W12 and D16 also abolished the protection of U2609 by TnaC-tRNA(Pro) against chemical methylation. These data indicate that the TnaC nascent peptide in the ribosome exit tunnel interacts with the U2609 nucleotide when the ribosome is Trp responsive. This interaction is affected by mutational changes in exit tunnel nucleotides of 23S rRNA, as well as in conserved TnaC residues, suggesting that they affect the structure of the exit tunnel and/or the nascent peptide configuration in the tunnel. PMID:22110039

  11. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S;

    2000-01-01

    The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...

  12. Retargeting FX-binding-ablated HAdV-5 to vascular cells by inclusion of the RGD-4C peptide in hexon hypervariable region 7 and the HI loop.

    Science.gov (United States)

    Robertson, Stacy; Parker, Alan L; Clarke, Carolyn; Duffy, Margaret R; Alba, Raul; Nicklin, Stuart A; Baker, Andrew H

    2016-08-01

    Recent studies have generated interest in the function of human adenovirus serotype 5 (HAdV-5) hexon:  factor X (FX) binding and subsequent hepatocyte transduction and interaction with the immune system. Here, we retargeted adenovirus serotype 5 vectors, ablated for FX interaction, by replacing amino acids in hexon HVR7 with RGD-4C or inserting the peptide into the fibre HI loop. These genetic modifications in the capsid were compatible with virus assembly, and could efficiently retarget transduction of the vector via the αvβ3/5 integrin-mediated pathway, but did not alter immune recognition by pre-existing human neutralizing anti-HAdV-5 antibodies or by natural antibodies in mouse serum. Thus, FX-binding-ablated HAdV-5 can be retargeted but remain sensitive to immune-mediated attack. These findings further refine HAdV-5-based vectors for human gene therapy and inform future vector development. PMID:27189759

  13. 不同的血糖水平对2型糖尿病C肽及并发症的影响%Influences of Different Blood Sugar Concentrations on C Peptide Level and Complication in Diabetes Type 2

    Institute of Scientific and Technical Information of China (English)

    胡新艳; 殷先德; 李云; 王文亮

    2001-01-01

    @@ 2型糖尿病(DM)在我国不仅是高发病,而且是影响人类健康的终身性及全身性疾病.本文仅对我院门诊及病房收治的2型DM近5年血糖水平不同对C肽、慢性并发症的影响进行探讨.

  14. C-peptide, IGF-I, sex-steroid hormones and adiposity : a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Bezemer, ID; Rinaldi, S; Dossus, L; van Gils, CH; Peeters, PHM; Noord, PAH; Bueno-de-Mesquita, HB; Johnsen, SP; Overvad, K; Olsen, A; Tjonneland, A; Boeing, H; Lahmann, PH; Linseisen, J; Nagel, G; Allen, N; Roddam, A; Bingham, S; Khaw, KT; Kesse, E; Tehard, B; Clavel-Chapelon, F; Agudo, A; Ardanaz, E; Quiros, [No Value; Amiano, P; Martinez-Garcia, C; Tormo, MJ; Pala, [No Value; Panico, S; Vineis, P; Palli, D; Tumino, R; Trichopoulou, A; Baibas, N; Zilis, D; Hemon, B; Norat, T; Riboli, E; Kaaks, R

    2005-01-01

    Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the Europe

  15. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S;

    2000-01-01

    (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ....002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P score increased significantly, indicating a deterioration in insulin sensitivity; whereas...

  16. Characteristics and relevant factors of insulin, C-peptide release after oral glucose tolerance test in newly diagnosed type 2 diabetes mellitus%初发2型糖尿病胰岛素C肽释放特点及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    谢媛; 马向华; 倪娟; 桑谊荃; 李晓娜; 俞岭

    2013-01-01

    目的 探讨初发2型糖尿病患者口服葡萄糖耐量实验和胰岛素、C肽变化特点及相关因素.方法 初发2型糖尿病患者192例,口服75 g葡萄糖耐量试验和胰岛素、C肽释放试验,分别在0、30、60、120、180分钟测定血糖、胰岛素和C肽.根据胰岛素和C肽高峰出现时间分为胰岛素C肽分泌高峰同步组和胰岛素C肽分泌高峰不同步组,使用稳态模型评估胰岛素抵抗程度、胰岛β细胞功能、Matsuda胰岛素敏感指数(Matsuda insulin sensitive index, Matsuda ISI)评估胰岛素敏感性.结果 胰岛素C肽分泌高峰比较,同步组与不同步组C肽高峰均在120分钟,不同步组胰岛素高峰在60分钟,同步组在120分钟;同步组120分钟胰岛素、C肽(35.54±28.98) mU/L、(2 317.02±973.21) pmol/L,高于不同步组(24.72±20.88) mU/L、(1 956.93±657.22) pmol/L;同步组C肽曲线下面积(3.15×10 5±1.21×105) pmol×min高于不同步组(2.82×10 5±8.62×104) pmol×min.结论 初发2型糖尿病行口服葡萄糖耐量实验和胰岛素、C肽释放实验显示,胰岛素、C肽释放高峰同步的患者实际胰岛素抵抗程度要高于不同步组,当两者不同步时,C肽释放试验更能反映2型糖尿病的真实病理生理状态.

  17. 重组leptin干预对营养性肥胖大鼠血清胰岛素、C-肽、内源性leptin含量及ob基因表达水平的影响%Effects of intracerebroventricular injection of leptin on the expression of obese gene in adipose tissue and the level of serum leptin and serum insulin, C-peptide in diet-induced obese rats

    Institute of Scientific and Technical Information of China (English)

    刘倩琦; 陈荣华; 郭锡熔; 费莉

    2005-01-01

    目的:探讨重组leptin侧脑室注射后,营养性肥胖大鼠模型腹膜后脂肪组织obese基因表达、内源性leptin含量以及血清胰岛素、C肽的变化,以期进一步探讨leptin中枢干预对肥胖大鼠leptin抵抗、胰岛素抵抗的改善作用.方法:(1)应用高营养饮食诱导的肥胖大鼠模型,用ELISA双抗体夹心法和放免法测定血清中leptin及胰岛素、C肽的含量;(2)应用RT-PCR技术检测各组大鼠脂肪组织中obese基因的表达水平.结果:(1)肥胖组大鼠经leptin干预后血清胰岛素和C肽明显降低,与正常各组之间无显著性差异;肥胖对照组、生理盐水组血清胰岛素、C肽较正常组明显升高.(2)肥胖大鼠经重组leptin干预后,脂肪组织ob mRNA含量明显低于肥胖对照组、肥胖生理盐水组;其与正常对照组、正常leptin、生理盐水干预组之间无显著性差异.(3)肥胖对照组、肥胖生理盐水组大鼠血清leptin含量明显高于肥胖leptin干预组以及正常对照组、正常各干预组;肥胖leptin干预组与正常对照组、正常各干预组之间无显著性差异.(4)各组大鼠脂肪组织中ob mRNA含量与其血清leptin含量、呈显著正相关关系.大鼠血清leptin含量与血清胰岛素、C肽浓度呈显著正相关.结论:侧脑室给予leptin可以显著减少肥胖大鼠脂肪组织中ob基因的表达以及血清leptin、胰岛素和C肽的含量,改善leptin和胰岛素抵抗.同时证实血清leptin含量与胰岛素、C肽的分泌密切相关,可能参与了leptin和胰岛素抵抗在肥胖发生中的作用.

  18. Effect of human proinsulin C-peptide on erythrocyte Na+-K+-ATPase activity and Ca2+concentration in patients with type H diabetes mellitus in vitro%胰岛素原C肽对2型糖尿病患者离体红细胞膜Na+-K+-ATP酶活性及红细胞内Ca2+浓度的影响

    Institute of Scientific and Technical Information of China (English)

    李素霞; 袁勤生

    2006-01-01

    目的研究外源性胰岛素原C肽对2型糖尿病患者离体红细胞膜Na+-K+-ATP酶活性及红细胞内Ca2+浓度的影响.方法取2型糖尿病患者空腹血,肝素抗凝,分离红细胞,生理盐水重新悬浮,加外源性C肽,分别测定细胞膜上的Na+-K+-ATP酶活性和细胞内Ca2+浓度.结果外源性C肽的加入可升高2型糖尿病患者红细胞膜的Na+-K+-ATP酶活性,并降低红细胞内的Ca2+浓度.结论胰岛素原C肽可以改善2型糖尿病患者降低的红细胞膜Na+-K+-ATP酶活性.

  19. Insulin resistance and breast-cancer risk.

    Science.gov (United States)

    Bruning, P F; Bonfrèr, J M; van Noord, P A; Hart, A A; de Jong-Bakker, M; Nooijen, W J

    1992-10-21

    Life-style has a major influence on the incidence of breast cancer. To evaluate the effects of life-style related metabolic-endocrine factors on breast cancer risk we conducted a case-control study comparing 223 women aged 38 to 75 years presenting with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer, who participated in a population-based breast cancer screening program. Women reporting diabetes mellitus were excluded. Sera from 110 women of the same age group presenting with early stage melanoma, lymphoma or cervical cancer were used as a second 'other-cancer control group'. Serum levels of C-peptide were significantly higher in early breast cancer cases compared to controls. The same was found for the ratios C-peptide to glucose or C-peptide to fructosamine, indicating insulin resistance. Sex hormone binding globulin was inversely, triglycerides and available estradiol were positively related to C-peptide. Serum C-peptide levels were related to body mass index (BMI), and to waist/hip ratio (WHR), in particular in controls. However, the relative increase of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was independent of BMI or WHR. The log relative risk was linearly related to the log C-peptide levels. Relative risk according to quintiles, and adjusted for age, family history, BMI and WHR, for women at the 80% level was 2.9 as compared with those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to fructosamine values were not observed in the sera from women belonging to the 'other-cancer control group'. This study suggests that hyperinsulinemia with insulin resistance is a significant risk factor for breast cancer independent of general adiposity or body fat distribution. PMID:1399128

  20. Specific and direct radioimmunoassay for human proinsulin in serum

    International Nuclear Information System (INIS)

    A routine radioimmunoassay for human proinsulin in serum has been developed. The reagents used were: antibodies against the C-peptide part of the proinsulin molecule, human proinsulin as the standard and 125I-labelled sythetic human Tyr-C-peptide as the tracer. (orig.)

  1. 儿童青少年糖尿病临床特征及初步分型探讨%Clinical characteristics and primary classification for diabetes in children and adolescents

    Institute of Scientific and Technical Information of China (English)

    范元硕; 罗建华; 于瑞萍; 刘波; 龙本丹

    2013-01-01

    Objective To investigate the clinical characteristics and primary classification of diabetes in children and adolescents. Methods According to fasting C-peptide level, 36 children and adolescents with diabetes were divided into two groups: decreased C-peptide group (fasting C-peptide level<0.60 μg/L, n=24) and normal C-peptide group (fasting C-peptide level≥0.60 μg/L, n=12). Clinical characteristics were compared between two groups. Results Compared with decreased C-peptide group, normal C-peptide group had significantly higher proportion of acanthosis nigricans, family history of type 2 diabetes, metabolic syndrome and overweight/obesity (P< 0.01 or P<0.05). The levels of body mass index, waist circumference, fasting C-peptide, postprandial C-peptide and A C-peptide in normal C-peptide group were significantly higher than those in decreased C-peptide group (all P<0.01). The rate of positive glutamic acid decarboxylase antibody/protein tyrosine phosphate antibody, concurrent ketosis/ke-toacidosis and underweight in normal C-peptide group was significantly lower than that in decreased C-peptide group. (P<0.01 or P<0.05) Normal C-peptide group showed significantly lower levels in random blood glucose and β hy-droxybutyric acid than those in decreased C-peptide group (P<0.01 or P<0.05). Conclusion According to fasting C-peptide level, children and adolescents with diabetes can be primary classified. Decreased C-peptide group is more likely to be classified as type 1 diabetes, and normal C-peptide group is more likely to be classified as type 2 diabetes.%目的 探讨儿童青少年糖尿病患者的临床特征和初步分型.方法 根据空腹C肽水平将36例儿童青少年糖尿病患者分为C肽降低组(空腹C肽<0.60 μg/L,24例)和C肽正常组(空腹C肽≥0.60 μg/L,12例),比较两组患者的临床资料.结果 C肽正常组黑棘皮症、2型糖尿病家族史、代谢综合征及超重/肥胖者的比例明显高于C肽降低组(P<0.01

  2. Metabolic effect of islet B-cell function in insulin-treated diabetes

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Iversen, S;

    1989-01-01

    We studied the relationship between endogenous insulin secretion and fasting levels of plasma free fatty acids (FFA), plasma acetoacetate plus plasma 3-hydroxybutyrate (total ketone bodies), blood glucose, and HbA1 in 132 diabetic outpatients treated with conventional insulin regimens. Patients.......60 nmol/l, and one group with C-peptide stimulation greater than 0.60 nmol/l. According to clinical criteria the prevalence of insulin-dependent diabetes mellitus was approximately 90% in patients with C-peptide stimulation less than 0.32 nmol/l, approximately 25% in patients with C-peptide stimulation...... were divided into four groups according to plasma C-peptide concentration after intravenous stimulation with glucagon: one group with C-peptide stimulation less than 0.06 nmol/l, one group with C-peptide stimulation 0.06- less than 0.32 nmol/l, one group with C-peptide stimulation 0.32- less than 0...

  3. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A;

    2000-01-01

    of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both......, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were...

  4. The reduction in hepatic insulin clearance after oral glucose is not mediated by gastric inhibitory polypeptide (GIP)

    DEFF Research Database (Denmark)

    Meier, Juris J; Gallwitz, Baptist; Siepmann, Nina;

    2003-01-01

    administration, plasma concentrations of total and intact GIP reached to peak levels of 80+/-7 and 54+/-5 pmol/l, respectively (prise in insulin after oral glucose and after intravenous GIP administration significantly exceeded the rise in C-peptide (p...Since the C-peptide/insulin ratio is reduced after oral glucose ingestion, the incretin hormone gastric inhibitory polypeptide (GIP) has been assumed to decrease hepatic insulin extraction. It was the aim of the present study to evaluate the effects of GIP on insulin extraction. Seventy...... the total integrated insulin and C-peptide concentrations (AUCs), only the oral glucose load (peffect does not appear to be mediated...

  5. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

    DEFF Research Database (Denmark)

    Kielgast, Urd; Holst, Jens Juul; Madsbad, Sten;

    2011-01-01

    without (C-peptide negative) were studied. All C-peptide-positive patients were treated with liraglutide plus insulin, whereas C-peptide-negative patients were randomly assigned to liraglutide plus insulin or insulin monotherapy. Continuous glucose monitoring with identical food intake and physical...... activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA(1c); time spent with blood glucose 10, and 3.9-9.9 mmol/L; and body weight were evaluated. RESULTS Insulin dose decreased from 0.50 ± 0.06 to 0.31 ± 0.08 units/kg per day (P ...-cell function at baseline, and two patients discontinued insulin treatment. In C-peptide-positive patients, time spent with blood glucose mean [range] -2.3 ± 0.3 kg [-0.5 to -5...

  6. Validation of methods for measurement of insulin secretion in humans in vivo

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A;

    2000-01-01

    of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both......). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method......, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were...

  7. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  8. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes

    DEFF Research Database (Denmark)

    Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg;

    2008-01-01

    OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study...... Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects...... completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were...

  9. The Proinsulin C-peptide—A Multirole Model

    OpenAIRE

    Steiner, Donald F.

    2004-01-01

    The C-peptide links the insulin A and B chains in proinsulin, providing thereby a means to promote their efficient folding and assembly in the endoplasmic reticulum during insulin biosynthesis. It then facilitates the intracellular transport, sorting, and proteolytic processing of proinsulin into biologically active insulin in the maturing secretory granules of the β cells. These manifold functions impose significant constraints on the C-peptide structure that are conserved in evolution. Afte...

  10. Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests.

    Science.gov (United States)

    Cavallini, G; Bovo, P; Zamboni, M; Bosello, O; Filippini, M; Riela, A; Brocco, G; Rossi, L; Pelle, C; Chiavenato, A

    1992-01-01

    Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

  11. Bound or free: interaction of the C-terminal domain of Escherichia coli single-stranded DNA-binding protein (SSB) with the tetrameric core of SSB.

    Science.gov (United States)

    Su, Xun-Cheng; Wang, Yao; Yagi, Hiromasa; Shishmarev, Dmitry; Mason, Claire E; Smith, Paul J; Vandevenne, Marylène; Dixon, Nicholas E; Otting, Gottfried

    2014-04-01

    Single-stranded DNA (ssDNA)-binding protein (SSB) protects ssDNA from degradation and recruits other proteins for DNA replication and repair. Escherichia coli SSB is the prototypical eubacterial SSB in a family of tetrameric SSBs. It consists of a structurally well-defined ssDNA binding domain (OB-domain) and a disordered C-terminal domain (C-domain). The eight-residue C-terminal segment of SSB (C-peptide) mediates the binding of SSB to many different SSB-binding proteins. Previously published nuclear magnetic resonance (NMR) data of the monomeric state at pH 3.4 showed that the C-peptide binds to the OB-domain at a site that overlaps with the ssDNA binding site, but investigating the protein at neutral pH is difficult because of the high molecular mass and limited solubility of the tetramer. Here we show that the C-domain is highly mobile in the SSB tetramer at neutral pH and that binding of the C-peptide to the OB-domain is so weak that most of the C-peptides are unbound even in the absence of ssDNA. We address the problem of determining intramolecular binding affinities in the situation of fast exchange between two states, one of which cannot be observed by NMR and cannot be fully populated. The results were confirmed by electron paramagnetic resonance spectroscopy and microscale thermophoresis. The C-peptide-OB-domain interaction is shown to be driven primarily by electrostatic interactions, so that binding of 1 equiv of (dT)35 releases practically all C-peptides from the OB-domain tetramer. The interaction is much more sensitive to NaCl than to potassium glutamate, which is the usual osmolyte in E. coli. As the C-peptide is predominantly in the unbound state irrespective of the presence of ssDNA, long-range electrostatic effects from the C-peptide may contribute more to regulating the activity of SSB than any engagement of the C-peptide by the OB-domain.

  12. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Yon Mi; Do, Young Soo; Lee, Moon Kyu; Shin, Sung Wook; Liu, Wei Chiang; Choo; Sung Wook; Choo, In wook [Sungkyunkwan University School of Mecidine, Seoul (Korea, Republic of)

    2003-06-01

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed.

  13. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    International Nuclear Information System (INIS)

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed

  14. Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

    International Nuclear Information System (INIS)

    The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice. Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells

  15. INFLUENCE OF ACUPUNCTURE ON INSULIN RESISTANCE IN OBESITY PATIENTS

    Institute of Scientific and Technical Information of China (English)

    YI Wei; XU Nenggui; JIN Rui

    2002-01-01

    Aims: To investigate the influence of acupuncture on insulin resistance in obesity patients. Methods: In treatment group, 20 obesity patients were treated with acupuncture of Neiguan (PC 6), Zusanli (ST 36), Daimai (GB 26), Sanyinjiao (SP 6), Zhongwan (CV 12), etc.. In control group, 12 normal volunteer subjects were observed.The obesity index, fasting blood sugar (FPG), plasma insulin (FINS) and C-peptide contents, and insulin sensitive index (ISI) were measured before and after acupuncture treatment. Results: Before treatment in comparison with control group, FPG, FINS and C-peptide of obesity patients were significant higher (P < 0.01 ), while ISI was considerably lower ( P< 0.01 ); after acupuncture treatment, the levels of plasma insulin and C peptide decreased obviously, ISI increased markedly (P < 0.01 ), and the obesity index was considerably improved with a total effective rate of 85 %.Conclusion: Acupuncture can alleviate obesity and improve insulin resistance.

  16. Glucose responsive insulin production from human embryonic germ (EG) cell derivatives

    International Nuclear Information System (INIS)

    Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and β-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes

  17. EFFECTS OF GLUCAGON ON ISLET β CELL FUNCTION IN PATIENTS WITH DIABETES MELLITUS

    Institute of Scientific and Technical Information of China (English)

    Tong Wang; Xin-hua Xiao; Wen-hui Li; Heng Wang; Qi Sun; Tao Yuan; Guo-hua Yang

    2008-01-01

    Objective To evaluate islet β cell response to intravenous glucagon ( a non-glucose secretagogne) stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra-venous injection of 1 mg of glucagon.Results Both fasting and 6-minute post-glucagnn-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0. 76 ± 0.36 ng/mL vs. 1.81 ± 0. 78 ng/mL, P < 0. 05 ; 0. 88 ± 0. 42 ng/mL vs.3.68 ±0.98 ng/mL, P <0. 05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fast-ing leveL In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2. 45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P <0. 05 ; 5.26±1.24 ng/mLvs. 2. 15±0. 76 ng/mL, P < 0. 05 ). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups ( r = 0. 76, P < 0. 05 ).Conclusions The 6-minute glucagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

  18. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    OpenAIRE

    Vanelli Maurizio; Hougaard Philip; Svensson Jannet; Fredheim Siri; Andersen Marie Louise M; Pörksen Sven; Nielsen Lotte B; Åman Jan; Mortensen Henrik B; Hansen Lars

    2011-01-01

    Abstract Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycem...

  19. Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion.

    OpenAIRE

    Robbins, D C; Shoelson, S E; Rubenstein, A H; Tager, H S

    1984-01-01

    Familial hyperproinsulinemia, a hereditary syndrome in which individuals secrete high amounts of 9,000-mol wt proinsulin-like material, has been identified in two unrelated cohorts. Separate analysis of the material from each of the two cohorts had suggested that the proinsulin-like peptide was a conversion intermediate in which the C-peptide remained attached to the insulin B-chain in one case, whereas it was a conversion intermediate in which the C-peptide remained attached to the insulin A...

  20. A mixed diet supplemented with l-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects

    DEFF Research Database (Denmark)

    Halschou-Jensen, Kia; Knudsen, Knud E Bach; Nielsen, Soren;

    2015-01-01

    different textures and a liquid meal with maltose supplemented with 0 and 20% L-arabinose. In addition, 1•5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results...... of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of L-arabinose added to sucrose drinks...

  1. Fasting and oral glucose-stimulated levels of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are highly familial traits

    DEFF Research Database (Denmark)

    Gjesing, Anette Marianne Prior; Ekstrøm, Claus Thorn; Eiberg, Hans Rudolf Lytchoff;

    2012-01-01

    Heritability estimates have shown a varying degree of genetic contribution to traits related to type 2 diabetes. Therefore, the objective of this study was to investigate the familiality of fasting and stimulated measures of plasma glucose, serum insulin, serum C-peptide, plasma glucose-dependent......Heritability estimates have shown a varying degree of genetic contribution to traits related to type 2 diabetes. Therefore, the objective of this study was to investigate the familiality of fasting and stimulated measures of plasma glucose, serum insulin, serum C-peptide, plasma glucose...

  2. Effects of limited food intake and vitamin C supplementation on pancreatic glucagon and insulin in guinea pigs

    OpenAIRE

    B. Kaplan; Gönül, B.; Erdogan, D; Elbeg, S

    2009-01-01

    The aim of this study was to investigate the effects of limited food intake (LFI) (24, 48 and 120 h) and a single i.p. dose of vitamin C supplementation (500 mg/kg) on serum glucose and C-peptide levels, and pancreatic insulin and glucagon levels in guinea pigs. The highest serum glucose levels were found after vitamin C supplementation plus LFI for 48 h (LFI 48). Serum C-peptide levels were not significantly affected by food limitation (LFI 24, LFI 48, or LFI 120) as compared with controls, ...

  3. Food and Insulin Effect on QT/QTC Interval of ECG

    Science.gov (United States)

    2014-08-19

    Effects of Different Meals on the QT/QTc Interval; Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use; C-Peptide Effects on the QT/QTc Interval; Moxifloxacin ECG Profile in Fed and Fasted State; Japanese vs. Caucasian TQT Comparison

  4. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide

  5. Extrapancreatic insulin effect of glibenclamide

    NARCIS (Netherlands)

    H.W. Mulder (H. W.); W. Schopman Sr. (W.); A-J. van der Lely (Aart-Jan)

    1991-01-01

    textabstractIn eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The r

  6. Reproducibility of beta-cell function estimates in non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Gjessing, H J; Damsgaard, E M; Matzen, L E;

    1988-01-01

    We evaluated the reproducibility of different estimates of endogenous insulin secretion in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM). Fasting blood glucose concentration was similar on the 2 days of study. The coefficients of variation of fasting plasma C-peptide, plasma C...

  7. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian;

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...

  8. Gene probes to detect cross-culture contamination in hormone producing cell lines

    DEFF Research Database (Denmark)

    Matsuba, I; Lernmark, A; Madsen, Ole Dragsbæk;

    1988-01-01

    -culture contamination to monitor inter-species as well as intra-species cross contamination. An insulin-producing cell-line, Clone-16, originally cloned from a human fetal endocrine pancreatic cell line did not produce human c-peptide as anticipated. DNA from these cells showed no hybridization to the human ALU...

  9. Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Knop, Filip Krag; Madsen, Anna;

    2014-01-01

    -dependent insulinotropic polypeptide (GIP) and higher postprandial levels of insulin, proinsulin, C-peptide and GIP. Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin...

  10. A soluble-phase proinsulin radioimmunoassay and its use in diagnosis of hypoglycaemia

    International Nuclear Information System (INIS)

    A soluble-phase proinsulin assay has been developed which does not require solid-phase antibody-binding. A human proinsulin standard curve is prepared in insulin-free and proinsulin-free plasma for comparison with unknown plasma samples. Proinsulin and insulin are bound with excess anti-insulin antiserum, and free C-peptide is removed by charcoal adsorption. The supernatant is then assayed using a routine C-peptide radioimmunoassay which utilises anti-C-peptide antiserum. The sensitivity of the assay (2 standard deviations above zero) is 9 pmol/L using 200 μL plasma sample. The assay is free from insulin cross-reactivity up to 100 mU/L and C-peptide up to 2000 pmol/L. Between-assay CV is 13% at 100 pmol/L. The assay has been used in subjects with hypoglycaemia of various aetiologies and has shown that a raised plasma proinsulin in the presence of hypoglycaemia can occur in sulphonylurea-induced and reactive hypoglycaemia as well as in insulinomas. After hyperglycaemic clamps at 7.5, 10 and 15 mmol/L glucose, type II diabetics both on and off sulphonylurea, were found to have lower proinsulin concentrations compared with normal subjects, commensurate with the diabetics' lower insulin responses. (author)

  11. Soluble-phase proinsulin radioimmunoassay and its use in diagnosis of hypoglycaemia

    Energy Technology Data Exchange (ETDEWEB)

    Naylor, B.A.; Matthews, D.R.; Turner, R.C.

    1987-07-01

    A soluble-phase proinsulin assay has been developed which does not require solid-phase antibody-binding. A human proinsulin standard curve is prepared in insulin-free and proinsulin-free plasma for comparison with unknown plasma samples. Proinsulin and insulin are bound with excess anti-insulin antiserum, and free C-peptide is removed by charcoal adsorption. The supernatant is then assayed using a routine C-peptide radioimmunoassay which utilises anti-C-peptide antiserum. The sensitivity of the assay (2 standard deviations above zero) is 9 pmol/L using 200 ..mu..L plasma sample. The assay is free from insulin cross-reactivity up to 100 mU/L and C-peptide up to 2000 pmol/L. Between-assay CV is 13% at 100 pmol/L. The assay has been used in subjects with hypoglycaemia of various aetiologies and has shown that a raised plasma proinsulin in the presence of hypoglycaemia can occur in sulphonylurea-induced and reactive hypoglycaemia as well as in insulinomas. After hyperglycaemic clamps at 7.5, 10 and 15 mmol/L glucose, type II diabetics both on and off sulphonylurea, were found to have lower proinsulin concentrations compared with normal subjects, commensurate with the diabetics' lower insulin responses.

  12. Proteins differentially expressed in human beta-cells-enriched pancreatic islet cultures and human insulinomas

    DEFF Research Database (Denmark)

    Terra, Letícia F; Teixeira, Priscila C; Wailemann, Rosangela A M;

    2013-01-01

    In view of the great demand for human beta-cells for physiological and medical studies, we generated cell lines derived from human insulinomas which secrete insulin, C-peptide and express neuroendocrine and islet markers. In this study, we set out to characterize their proteomes, comparing them t...

  13. Hypoglycaemia associated with anorexia nervosa.

    OpenAIRE

    Fonseca, V; Ball, S; Marks, V; Havard, C W

    1991-01-01

    A 41 year old woman with severe emaciation due to longstanding anorexia nervosa presented with recurrent hypoglycaemia. During an episode of hypoglycaemia, serum insulin and C peptide were undetectable and plasma beta hydroxybutyrate, free fatty acids and lactate were inappropriately low. Response to intravenous glucagon was poor. Muscle enzymes were grossly elevated until she gained weight. Hypoglycaemia was abolished by weight gain.

  14. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    R.J. Strawbridge (Rona); J.R. Petrie (John); T. Forsen (Tom); C. Cooper (Cyrus); M. Franzosi; A. Hamsten (Anders); E. Ferrannini (Ele); M.S. Rios; C.-G. Östenson (Claes-Göran); K. Makrilakis (Konstantinos); T.J. Forsen (Tom); C. Osmond (Clive); C. Cooper (Charles); E.M. Dennison (Elaine); K. Jameson (Karen); A.A. Sayer; T. Kuulasmaa (Teemu); A. Stancáková (Alena); L. Lind (Lars); M.N. Mannila (Maria Nastase); H. Gu (Harvest); B. Zethelius (Björn); F. Turrini (Fabiola); R.J.F. Loos (Ruth); L. Pascoe (Laura); A.C. Syvanen; E. Ahlqvist (Emma); M. Horikoshi (Momoko); D. Barnes (Daniel); C. Han (Chen); A.K. Manning (Alisa); D. Rybin (Denis); S. Kanoni (Stavroula); A.M. Barker (Adam); W. Xie (Weijia); E. Eury (Elodie); J. Kerr-Conte (Julie); F. Pattou (François); P.R.V. Johnson (Paul); M. Travers (Mary); R.R. Frants (Rune); P. Eriksson (Per); L. Folkersen (Lasse); F.M. van't Hooft (Ferdinand); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steve); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noisël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); A.L. Elliott (Amanda); C. Fox (Craig); C.S. Franklin (Christopher); M. Ganser (Martha); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); A.U. Jackson (Anne); P.R.V. Johnson (Paul R.); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John R.); A.K. Petersen; C.P. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G. Bragi Walters (G.); M.N. Weedon (Michael); C. Wijmenga (Cisca); R.N. Bergman (Richard); S. Cauchi (Stephane); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); D. Hunter (David); K. Hveem (Kristian); K.L. Mohlke (Karen); A.D. Morris (Andrew); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); M. Walker (Mark); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); M.J. Daly (Mark); A.T. Hattersley (Andrew); F. Hu; J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); J.C. Florez (Jose); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James F); T. Illig (Thomas); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); E.K. Speliote (Elizabeth); C.J. Wille (Cristen); S.I. Bernd (Sonja); K.L. Mond (Keri); G. Thorleifsso (Gudmar); H. Lango Allen (Hana); C.M. Lindgre (Cecilia); J. Lua (Jian'an); R. Mäg (Reedik); J.C. 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Pietilainen (Kirsi Hannele); C. Platou (Carl); O. Polasek (Ozren); A. Pouta (Anneli); S. Rafelt (Suzanne); O. Raitakari (Olli); N.W. Rayner (Nigel William); M. Ridderstråel (Martin); W. Rief (Winfried); A. Ruokonen (Aimo); N.R. Robertson (Neil); P. Rzehak (Peter); V. Salomaa (Veikko); A.R. Sanders (Alan); M.S. Sandhu (Manjinder); S. Sanna (Serena); J. Saramies (Jouko); M.J. Savolainen (Markku); A. Scherag (Andre); S. Schipf (Sabine); S. Schreiber (Stefan); H. Schunkert (Heribert); K. Silander (Kaisa); J. Sinisalo (Juha); J.H. Smit (Jan); N. Soranzo (Nicole); U. Sovio (Ulla); J. Stephens (Jonathan); I. Surakka (Ida); A.J. Swift (Amy); M.L. Tammesoo; J.-C. Tardif (Jean-Claude); M. Teder-Laving (Maris); T.M. Teslovich (Tanya); J.R. Thompson (John); B. Thomson (Brian); A. Tönjes (Anke); J.B.J. van Meurs (Joyce); G.J.B. van Ommen; V. Vatin (Vincent); J. Viikari (Jorma); S. Visvikis-Siest (Sophie); V. Vitart (Veronique); C.I. Vogel (Carla); B.F. Voight (Benjamin); L. Waite (Lindsay); H. 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Horne (Benjamin); T. Illig (Thomas); C. Iribarren (Carlos); G.T. Jones (Gregory); J.W. Jukema (Jan Wouter); M.A. Kaiser (Michael); L.M. Kaplan (Lee); J.J.P. Kastelein (John); K-T. Khaw (Kay-Tee); J.W. Knowles (Joshua); G. Kolovou (Genovefa); A. Kong (Augustine); R. Laaksonen (Reijo); D. Lambrechts (Diether); K. Leander (Karin); G. Lettre (Guillaume); X. Li (Xiaohui); W. Lieb (Wolfgang); C. Loley (Christina); A.J. Lotery (Andrew); P.M. Mannucci (Pier); S. Maouche (Seraya); N. Martinelli (Nicola); P.P. McKeown (Pascal); C. Meisinger (Christa); T. Meitinger (Thomas); P.A. Merlini (Pier Angelica); V. Mooser (Vincent); T. Morgan (Thomas); T.W. Mühleisen (Thomas); J.B. Muhlestein (Joseph); T. Munzel (Thomas); K. Musunuru (Kiran); J. Nahrstaedt (Janja); C.P. Nelson (Christopher P.); M.M. Nöthen (Markus); O. Olivieri (Oliviero); R.S. Patel (Riyaz); C.C. Patterson (Chris); F. Peyvandi (Flora); L. Qu (Liming); A.A. Quyyumi (Arshed); D.J. Rader (Daniel); L.S. Rallidis (Loukianos); C. 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Ouwehand (Willem); A. Hall (Anne); J.R. Thompson (John); K. Stefansson (Kari); R. Roberts (Robert); U. Thorsteinsdottir (Unnur); C.J. O'Donnell (Christopher); R. McPherson (Ruth); N.J. Samani (Nilesh); J. Hopewell; S. Parish (Sharon); A. Offer (Alison); L. Bowman; P. Sleight (Peter); S. Armitage (Shane); R. Peto (R.); R. Collins (Rory); J.C. Chambers (John); N. Ahmed (Nabeel); M. Caulfield (Mark); P. Donnelly (Peter); P. Elliott (Paul); P. Froguel (Philippe); M.I. McCarthy (Mark); N.J. Samani (Nilesh); J. Scott (James); J.S. Sehmi (Joban); W. Zhang (Weihua); J.S. Kooner (Jaspal); R.J. Strawbridge (Rona); M. Sabater-Lleal (Maria); A. Mälarstig (Anders); B. Sennblad (Bengt); J. Öhrvik (John); A. Silveira (Angela); F. van't Hooft (Ferdinand); P. Eriksson (Per); A. Hamsten (Anders); M.-L. Hellénius (Mai-Lis); G. Olsson; S. Rust (Stephan); G. Assmann (Gerd); U. Seedorf (Udo); S. Barlera (Simona); M.G. Franzosi; G. Tognoni; R. Clarke (Robert); P. Linksted (Pamela); J. Hopewell; F.S. Collins (Francis); J. Peden (John); A. Goel (Anuj); H. Ongen (Halit); T. Kyriakou (Theodosios); F. Green (Fiona); M. Farrall (Martin); H. Watkins (Hugh); D. Saleheen; A. Rasheed (Asif); M.A. Zaidi (Aghar); N. Shah (Nisha); M. Samuel (Maria); C.B. Mallick (Chandana Basu); M. Azhar (Muhammad); K.S. Zaman (Khan Shah); A. Samad (Adbus); M. Ishaq (Muhammad); A. Gardezi (Ali); F.-R. Memon (Fazal-ur-Rehman); N.J. Samani (Nilesh); R. Frossard; P. Deloukas (Panagiotis); J. Danesh (John)

    2011-01-01

    markdownabstractOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new

  15. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josee; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Teresa Martinez-Larrad, Maria; Narisu, Narisu; Mannila, Maria Nastase; Ohrvik, John; Osmond, Clive; Pascoe, Laura; Payne, Felicity; Sayer, Avan A.; Sennblad, Bengt; Silveira, Angela; Stancakova, Alena; Stirrups, Kathy; Swift, Amy J.; Syvanen, Ann-Christine; Tuomi, Tiinamaija; van 't Hooft, Ferdinand M.; Walker, Mark; Weedon, Michael N.; Xie, Weijia; Zethelius, Bjorn; Ongen, Halit; Malarstig, Anders; Hopewell, Jemma C.; Saleheen, Danish; Chambers, John; Parish, Sarah; Danesh, John; Kooner, Jaspal; Ostenson, Claes-Goran; Lind, Lars; Cooper, Cyrus C.; Serrano-Rios, Manuel; Ferrannini, Ele; Forsen, Tom J.; Clarke, Robert; Franzosi, Maria Grazia; Seedorf, Udo; Watkins, Hugh; Froguel, Philippe; Johnson, Paul; Deloukas, Panos; Collins, Francis S.; Laakso, Markku; Dermitzakis, Emmanouil T.; Boehnke, Michael; McCarthy, Mark I.; Wareham, Nicholas J.; Groop, Leif; Pattou, Francois; Gloyn, Anna L.; Dedoussis, George V.; Lyssenko, Valeriya; Meigs, James B.; Barroso, Ines; Watanabe, Richard M.; Ingelsson, Erik; Langenberg, Claudia; Hamsten, Anders; Florez, Jose C.

    2011-01-01

    OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  16. Serum Level of the Adipokine “Vaspin” in Relation to Metabolic Parameters: Short – Term Effect of Specific Dietary Therapy

    Directory of Open Access Journals (Sweden)

    Maha I. A. Moaty

    2014-06-01

    CONCLUSION: The effect of the dietary supplements may play a role in alleviating the impact of the components of the MetS and may also sustain the level of the vaspin in the sensitization of the C-peptide in order to attain glucose homeostasis.

  17. Associations between Vitamin D Status and Type 2 Diabetes Measures among Inuit in Greenland May Be Affected by Other Factors

    DEFF Research Database (Denmark)

    Nielsen, Nina O; Bjerregaard, Peter; Rønn, Pernille F;

    2016-01-01

    study were included. Fasting- and 2hour plasma glucose and insulin, C-peptide and HbA1c were measured, and associations with serum 25(OH)D3 were analysed using linear and logistic regression. A subsample of 330 individuals who also donated a blood sample in 1987, were furthermore included. RESULTS...

  18. GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Mentis, Nikolaos; Vardarli, Irfan; Köthe, Lars D;

    2011-01-01

    , and placebo were administered over 360 min after an overnight fast (=1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined. RESULTS Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.......2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further...... enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07). CONCLUSIONS GIP is unable to...

  19. Effect of 5'-flanking sequence deletions on expression of the human insulin gene in transgenic mice

    DEFF Research Database (Denmark)

    Fromont-Racine, M; Bucchini, D; Madsen, O;

    1990-01-01

    Expression of the human insulin gene was examined in transgenic mouse lines carrying the gene with various lengths of DNA sequences 5' to the transcription start site (+1). Expression of the transgene was demonstrated by 1) the presence of human C-peptide in urine, 2) the presence of specific tra...... of the transgene was observed in cell types other than beta-islet cells.......Expression of the human insulin gene was examined in transgenic mouse lines carrying the gene with various lengths of DNA sequences 5' to the transcription start site (+1). Expression of the transgene was demonstrated by 1) the presence of human C-peptide in urine, 2) the presence of specific......, and -168 allowed correct initiation of the transcripts and cell specificity of expression, while quantitative expression gradually decreased. Deletion to -58 completely abolished the expression of the gene. The amount of human product that in mice harboring the longest fragment contributes up to 50...

  20. Extrapancreatic insulin effect of glibenclamide.

    Science.gov (United States)

    Mulder, H; Schopman, W; van der Lely, A J

    1991-01-01

    In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more prolonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide. PMID:1904820

  1. Comprehensive evaluation of pancreatic function in insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    The time course of the concentration of immunoreactive insulin (IRI) and C-peptide in the plasma and erythrocytes and the blood sugar level in GTT per os were investigated by means of radioimmunoassay. Altogether 73 healthy persons and 52 patients with a severe form of insulin-dependent diabetes mellitus were examined. To define the time course of changes in the concentration of the above values a rate gradient determined as a difference of changed concentration rate for the 1st and 2nd hour after load for each examined person, was proposed. The gradients of plasma IRI, plasma and erythrocytic C-peptide had maximum difference in healthy persons and patients. The hormone and blood sugar levels characterized the condition of the examined persons, and rate gradients were indicative of the state of the blood sugar regulation system

  2. Observations on the presence of insulin resistance in patients with essential hypertension and coronary heart disease

    International Nuclear Information System (INIS)

    Objective: To investigate the presence of insulin resistance in patients with essential hypertension (EH) and coronary heart disease (CHD). Methods: Fasting and 2h post oral 75g glucose blood sugar (with oxidase method), insulin and C-peptide (with RIA) levels were examined in 52 patients with EH, 40 patients with CHD and 35 controls. Results: The fasting and 2h post o- ral glucose serum levels of glucose, insulin and C-peptide in the patients were significantly higher than those in the controls (P < 0.01), suggesting presence of impaired glucose tolerance and insulin resistance. Conclusion: Impaired glucose tolerance due to insulin resistance was demonstrated in the studied patients with EH or CHD. (authors)

  3. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis

    DEFF Research Database (Denmark)

    Mortensen, H.B.; Swift, P.G.F.; Holl, R.W.;

    2010-01-01

    Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D). Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal......-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally. Results: Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12...... months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p

  4. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, L. B.; Porksen, S.; Andersen, M. L. M.;

    2011-01-01

    type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA(1c)), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA...... variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide) and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results: A repeated measurement...... model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03) for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002), which did not influence the association...

  5. Insulin Autoimmune Syndrome Associated with the Use of Thiocolchicoside: A Case report

    Directory of Open Access Journals (Sweden)

    Fettah ACIBUCU

    2016-03-01

    Full Text Available Insulin autoimmune syndrome (IAS is a disease characterized by hypoglycemia and insulin antibodies without insulin usage. We report the case of a patient diagnosed with IAS that was associated with the use of thiocolchicoside. A 62-year-old female patient was admitted to our clinic with fasting and postprandial hypoglycemia symptoms. She had a fasting glucose level of 47mg/dl, and high insulin, C-peptide and insulin antibody levels were detected. However, she had no signs of hypoglycemia during a 72 hour fasting test. In addition, the patient had used thiocolchicoside for a week a month prior to the beginning of her symptoms, but she was not taking any insulin or diabetic medications. A diagnosis of IAS was made, and the patient was put on an appropriate diet. Three months following this diagnosis, the patient’s complaints have minimilized, and the insulin and C-peptide levels have decreased.

  6. Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

    Directory of Open Access Journals (Sweden)

    Silke A Herzberg-Schäfer

    Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

  7. Molecular basis for the ribosome functioning as an L-tryptophan sensor.

    Science.gov (United States)

    Bischoff, Lukas; Berninghausen, Otto; Beckmann, Roland

    2014-10-23

    Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC) adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2), thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation. PMID:25310980

  8. Molecular Basis for the Ribosome Functioning as an L-Tryptophan Sensor

    Directory of Open Access Journals (Sweden)

    Lukas Bischoff

    2014-10-01

    Full Text Available Elevated levels of the free amino acid L-tryptophan (L-Trp trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2, thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation.

  9. Persistent Hypoglycemia in Patient with Hodgkin’s Disease

    OpenAIRE

    Harold Cinco Lim; Lubna Bashir Munshi; David Sharon

    2015-01-01

    Hypoglycemia is a rare complication of Hodgkin’s disease. Several explanations have been postulated but the exact pathophysiology is not well understood. We are presenting a case of newly diagnosed Stage IV Hodgkin’s disease that developed persistent and recurrent hypoglycemia despite giving glucagon, repeated 50% dextrose, and D5 and D10 continuous infusion. Hypoglycemia workup showed the C-peptide level to be low. Patient was suspected of having hypoglycemia related to lymphoma and was give...

  10. 妊娠21週時に劇症1型糖尿病を発症し重症急性膵炎を合併した1例

    OpenAIRE

    丸山, 雅史; 小松, 健一; 浜野, 英明; 越知, 泰英; 宮林, 秀晴; 青木, 雄次; 吉澤, 要; 川, 茂幸; 清澤, 研道

    2006-01-01

    A 30-year-old woman was admitted because of severe thirst and polyuria at 21 weeks of gestation. After fetal demise, she developed disturbance of consciousness. Laboratory examinations showed hyperglycemia, ketoacidosis, low urinary C-peptide concentration, an almost normal HbA1c level, undetectable diabetesrelated autoantibodies, and high serum pancreatic amylase. These findings indicated fulminant type 1 diabetes mellitus. Hyperamylasemia and diffuse swelling of the pancreas associated with...

  11. Lebertransplantation und Stoffwechselprozesse

    OpenAIRE

    Nolting, Sabine Edith

    2012-01-01

    Liver transplantation is a common therapy of end stage liver disease. The aim of this study was to investigate metabolic pathways on the model of living-donor liver transplantation. Donors and recipients of liver transplantation underwent an insulin modified intravenous glucose tolerance test (ivGTT) at four points in time.121 With the minimal model technique insulin sensitivity, glucose effectiveness and ß-cell secretion have been calculated.15 Fasting glucose, insulin, c-peptid, proinsul...

  12. Case Report: When an Induced Illness Looks Like a Rare Disease.

    Science.gov (United States)

    Rabbone, Ivana; Galderisi, Alfonso; Tinti, Davide; Ignaccolo, Maria Giovanna; Barbetti, Fabrizio; Cerutti, Franco

    2015-11-01

    The recognition of fabricated illness (FI) in a child represents a diagnostic challenge. The suspicion of FI often arises from the discrepancy between laboratory tests and clinical history. For instance, (unnecessary) insulin injections by caregivers has been widely described as a common cause of factitious hypoglycemia that may be inferred from discrepancies between plasma insulin and c-peptide. However, contemporary administration of insulin with an insulin secretagogue (glyburide), and of additional drugs, can make the diagnostic pathway problematic. We report the case of a child 4 years and 11 months old, admitted for alternance of hypo- and hyperglycemia associated with hirsutism, hypokalemia, nephrocalcinosis, and neurodevelopmental delay. All these features were compatible with Rabson-Mendenhall syndrome, a rare disorder of severe insulin resistance linked to mutations of insulin receptor. At admission, plasma insulin levels were high during hypoglycemic episodes, but c-peptide was repeatedly in the normal range. The genetic analysis of insulin receptor was negative. The story of previous hospital admissions, inconsistency between insulin and c-peptide values, and association between hypoglycemic episodes in the child with the presence of the mother, raised the suspicion of FI. This hypothesis was confirmed by a video recording that revealed the administration by the mother of multiple drugs (insulin, glyburide, progesterone, and furosemide) that mimicked most of the features of Rabson-Mendenhall syndrome, including hirsutism and hypoglycemia with coincident, inappropriately normal c-peptide values due to the administration of the insulin secretagogue. Our case indicates that inconsistency among consecutive diagnostic tests should be regarded as a clue of FI.

  13. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

    Science.gov (United States)

    Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

    2010-11-01

    Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

  14. Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Stephens, J W; Bodvarsdottir, T B; Wareham, K;

    2011-01-01

    .9%) and glibenclamide (1.0%, 2.2 mmol/L, 2.5 mmol/L, 17.5%). Repaglinide was also associated with an increase in the AUC60 and AUC120 for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1...

  15. Hypoglycemia Secondary to Sulfonylurea Ingestion in a Patient with End Stage Renal Disease: Results from a 72-Hour Fast

    Directory of Open Access Journals (Sweden)

    Alice Abraham

    2015-01-01

    Full Text Available Insulin, proinsulin, and C-peptide levels increase with sulfonylurea exposure but the acuity of increase has not been described in dialysis patients. We present a case of a dialysis patient who presented with hypoglycemia and was found to have accidental sulfonylurea ingestion. This is a 73-year-old man with ESRD on peritoneal dialysis, without history of diabetes, who presented with hypoglycemia. Past medical history includes multiple myeloma, congestive heart failure, and hypertension. At initial presentation, his blood glucose was 47 mg/dL, with concomitant elevations in the following: C-peptide 30.5 (nl: 0.8–3.5 ng/mL, insulin 76 (nl: 3–19 μIU/mL, and proinsulin 83.3 (nl: ≤8.0 pmol/L. During the 72-hour fast, which he completed without hypoglycemia, insulin declined to be within normal limits (to 12 μIU/mL; proinsulin (to 12.1 pmol/L and C-peptide (to 7.2 ng/mL levels decreased but remained elevated. The sulfonylurea screen ultimately returned positive for glipizide, clinching the diagnosis. This is the first reported case which characterizes the chronic elevation of proinsulin in a patient with ESRD, as well as its dramatic increase after a presumed solitary exposure to sulfonylurea. The 72-hour fast conducted gives insight into the clearance of insulin, proinsulin, and C-peptide after sulfonylurea ingestion in ESRD.

  16. Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

    OpenAIRE

    Nanjo, K; Sanke, T; Miyano, M; Okai, K.; Sowa, R; Kondo, M.; Nishimura, S; Iwo, K; Miyamura, K; Given, B D

    1986-01-01

    We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration...

  17. Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

    OpenAIRE

    Gray, R S; Cowan, P.; Di Mario, U.; Elton, R A; Clarke, B F; Duncan, L J

    1985-01-01

    Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in t...

  18. Conversion of proinsulin to insulin occurs coordinately with acidification of maturing secretory vesicles

    OpenAIRE

    1986-01-01

    Proinsulin is a single polypeptide chain composed of the B and A subunits of insulin joined by the C-peptide region. Proinsulin is converted to insulin during the maturation of secretory vesicles by the action of two proteases and conversion is inhibited by ionophores that disrupted intracellular H+ gradients. To determine if conversion of prohormone to hormone actually occurs in an acidic secretory vesicle, cultured rat islet cells were incubated in the presence of 3-(2,4- dinitroanilino)-3'...

  19. Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

    OpenAIRE

    Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

    2012-01-01

    Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. W...

  20. Reversed-phase high-performance liquid chromatographic analyses of insulin biosynthesis in isolated rat and mouse islets

    DEFF Research Database (Denmark)

    Linde, S; Hansen, Bruno A.; Welinder, B S;

    1989-01-01

    Two RP-HPLC systems were developed for the separation of the products of the conversion of proinsulin into insulin in rat and mouse islets, including proinsulin I and II. Peaks were identified by microsequencing and radiosequencing. It was confirmed that mouse C-peptide I has a two amino acid...... of the stored insulin, indicating a slower conversion rate of proinsulin II compared to proinsulin I....

  1. In Vivo Misfolding of Proinsulin Below the Threshold of Frank Diabetes

    OpenAIRE

    Hodish, Israel; Absood, Afaf; Liu, Leanza; Liu, Ming; Haataja, Leena; Larkin, Dennis; Al-Khafaji, Ahmed; Zaki, Anthony; Arvan, Peter

    2011-01-01

    OBJECTIVE Endoplasmic reticulum (ER) stress has been described in pancreatic β-cells after onset of diabetes—a situation in which failing β-cells have exhausted available compensatory mechanisms. Herein we have compared two mouse models expressing equally small amounts of transgenic proinsulin in pancreatic β-cells. RESEARCH DESIGN AND METHODS In hProCpepGFP mice, human proinsulin (tagged with green fluorescent protein [GFP] within the connecting [C]-peptide) is folded in the ER, exported, co...

  2. Insulin sensitivity and β-cell function in normoglycemic offspring of individuals with type 2 diabetes mellitus: Impact of line of inheritance

    Directory of Open Access Journals (Sweden)

    Edavan P Praveen

    2012-01-01

    Full Text Available Aims: The aim was to study the effect of family history of type 2 diabetes mellitus (T2DM on insulin sensitivity and b-cell function in normoglycemic offspring. Material and Methods: Offspring of T2DM patients (cases and individuals without family history of T2DM (controls were the subjects for this cross-sectional study. All participants underwent 75 g OGTT and samples were collected for plasma insulin, C-peptide, and proinsulin at 0, 30, 60, and 120 minutes. Results: A total of 271 cases (age 22 ± 10 years; 53% males and 259 controls (28 ± 10 years, 66% males were enrolled for the study. BMI, plasma insulin, C-peptide, proinsulin, HOMA-IR, and insulinogenic index (0-120 were significantly higher and whole-body insulin sensitivity (WBISI and disposition index (0-120 [DI 120] were lower in cases compared to controls. After adjusting for BMI, proinsulin at 120 minutes, area under the curve (AUC of proinsulin (during OGTT and AUC proinsulin/AUC C-peptide were significantly higher in cases. Cases were subdivided into four groups according to inheritance pattern; paternal DM (PDM, maternal DM (MDM, grandparental DM (GPDM, and both parents DM (BPDM. The magnitude of differences varied with relationship (greater when both parents and grandparents were affected. Mean HOMA-IR was higher by 127% and 50% and DI 120 was lower by 33% and 18% (adjusted for age and gender in the BPDM and GPDM groups respectively compared to controls. Conclusions: We observed higher BMI, plasma insulin, C-peptide, and proinsulin and lower insulin sensitivity and b-cell compensation in normoglycemic offspring of T2DM subjects compared to controls. Differences were greater when both parents and grandparents had T2DM.

  3. Identification of a Small Molecular Anti - HIV - 1 Compound that Interferes with Formation of the Fusion - active gp41 Core

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The human immunodeficiency virus type 1 (HIV - 1 ) envelope glycoprotein gp41 plays a critical role in the fusion of viral and target cell membranes. The gp41 extracellular domain, which contains fusion peptide (FP), N - and C - terminal hydrophobic heptad repeats (NHR and CHR, respectively). Peptides derived from NHR and CHR regions,designated N- and C- peptides, respectively, can interact with each other to form a six - stranded coiled - coil domain, representing the fusion-active gp41 core. Our previous studies demonstrated that the C- peptides have potent inhibitory activity against HIV- 1 infection.These peptides inhibit HIV- 1 -mediated membrane fusion by binding to NHR regions for preventing the formation of fusion- active gp41 core. One of the C - peptides, T - 20, which is in the phase Ⅲ clinical trails, is expected to become the first peptide HIV fusion inhibitory drug in the near future. However, this peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Therefore, it is essential to develop small molecular non -peptide HIV fusion inhibitors having similar mechanism of action as the C- peptides. We have established an ELISA- based screening assay using a unique monoclonal antibody, NC- 1, which can specifically bind to a conformational epitope on the gp41 core domain. Using this screening assay, we have identified a small molecular anti- HIV- 1 compound,named ADS-Jl, which inhibits HIV- 1- mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion - active gp41 core. This compound will be used as a lead to design and develop novel HIV fusion inhibitors as new drugs for the treatment of HIV infection and/or AIDS.

  4. Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes: a randomised cross-over trial

    OpenAIRE

    Fontes-Villalba, Maelán; Lindeberg, Staffan; Granfeldt, Yvonne; Knop, Filip K.; Memon, Ashfaque A.; Carrera-Bastos, Pedro; Picazo, Óscar; Chanrai, Madhvi; Sunquist, Jan; Sundquist, Kristina; Jönsson, Tommy

    2016-01-01

    Background We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods In a r...

  5. Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting

    DEFF Research Database (Denmark)

    Højlund, Kurt; Wildner-Christensen, M; Eshøj, O;

    2001-01-01

    To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P ... of counterregulatory factors increased during the fast [P fasting (P ... decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P

  6. The 10th quality control survey for radioisotope in vitro tests in Japan, 1988

    Energy Technology Data Exchange (ETDEWEB)

    1989-10-01

    This report presents the results of the 10th quality control nationwide survey. Of 780 selected facilities, 471 (60.4%) participated in this survey. Items examined were as follows: alpha-fetoprotein (AFP), aldosterone; beta microglobulin, carbohydrate antigen (CA) 15-3, C peptide, digoxin, elastase 1, free triiodothyronine (FT{sub 3}), gastrin, growth hormone, human chorionic gonadotropin (HCG), immunoglobulin E, prostatic acid phosphatase (PAP), pancreatic secretory trypsin inhibitor, progesterone, prolactine, thyroglobulin, triiodothyronine (T{sub 3}), triiodothyronine uptake (T{sub 3} U), tissue polypeptide antigen (TPA), thyroid stimulating hormone (TSH), and testosterone. 'Within kit variation' between facilities showed a coefficient of variation (CV) of more than 15% for AFP, FT , gastrin, HCG, progesterone, prolactine II, thyroglobulin, and TSH; and 'between kit variation' showed a CV of more than 15% for AFP, aldosterone, gastrin, IgE, PAP, progesterone, prolactin II, thyroglobuline, TSH, and testosterone. In comparing annual changes in CV, the following items were improved: aldosterone, C-peptide, gastrin, TPA, and TSH for 'within kit variation'; andaldosterone, C-peptide, gastrin, T{sub 3}, T{sub 3} U, TSH, and testosterone for 'between kit variation'. (N.K.).

  7. An effective conjugation strategy for designing short peptide-based HIV-1 fusion inhibitors.

    Science.gov (United States)

    Liang, Guodong; Wang, Huixin; Chong, Huihui; Cheng, Siqi; Jiang, Xifeng; He, Yuxian; Wang, Chao; Liu, Keliang

    2016-08-16

    Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins. PMID:27454320

  8. Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Tsai Pei-Jiun

    2012-04-01

    Full Text Available Abstract Background Although diabetes mellitus (DM can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats. Methods MSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly. Results Human nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic β-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver. Conclusion Thus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.

  9. Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

    Science.gov (United States)

    Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

    2015-10-01

    In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide 1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE.

  10. Epidemiological Pattern of Newly Diagnosed Children with Type 1 Diabetes Mellitus, Taif, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Naglaa Mohamed Kamal Alanani

    2013-01-01

    Full Text Available Introduction and Aim. Type-1-diabetes mellitus (T1DM is the most commonly diagnosed type of DM in children and adolescents. We aim to identify the epidemiological profile, risk factors, clinical features, and factors related to delayed diagnosis or mismanagement in children with newly diagnosed T1DM in Taif, Saudi Arabia. Patients and Methods. Ninety-nine newly diagnosed patients were included in the study along with 110 healthy controls. Patients were classified into 3 groups (I: >2 years, II: 2–>6 years, and III: 6–12 years. Both patients and controls were tested for C-peptide, TSH, and autoantibodies associated with DM and those attacking the thyroid gland. Results. Diabetic ketoacidosis was present in 79.8%. Delayed and missed diagnoses were recorded in 45.5%, with significant correlation to age and district of origin. Severity at presentation showed significant correlation with age and cow’s milk feeding. Group I, those with misdiagnosis or positive DM related autoantibodies, had more severe presentations. The correlation of C-peptide and TSH levels in patients and controls was significant for C-peptide and nonsignificant for TSH. Conclusion. Misdiagnosis and mismanagement are common and account for more severe presentation, especially in young children >2 years. Early introduction of cow’s milk appears to be a risk factor for the development of T1DM.

  11. Effects of limited food intake and vitamin C supplementation on pancreatic glucagon and insulin in guinea pigs

    Directory of Open Access Journals (Sweden)

    B Kaplan

    2009-08-01

    Full Text Available The aim of this study was to investigate the effects of limited food intake (LFI (24, 48 and 120 h and a single i.p. dose of vitamin C supplementation (500 mg/kg on serum glucose and C-peptide levels, and pancreatic insulin and glucagon levels in guinea pigs. The highest serum glucose levels were found after vitamin C supplementation plus LFI for 48 h (LFI 48. Serum C-peptide levels were not significantly affected by food limitation (LFI 24, LFI 48, or LFI 120 as compared with controls, but when vitamin C was supplemented, the C-peptide levels were moderately enhanced. Immunohistochemical findings on pancreatic islets showed increased staining intensity for both insulin and glucagon when vitamin C was supplemented. In addition, the alpha and beta cells were stimulated, particularly by vitamin C supplementation plus LFI 120. Based on these findings, vitamin C supplementation may have a beneficial effect on the alpha and beta cells.

  12. Methods in Analyzing Abdominal Fat of Obese Children and Adolescents%肥胖儿童青少年腹部脂肪不同评价方法比较

    Institute of Scientific and Technical Information of China (English)

    郑小斐; 汤庆娅; 陶晔璇

    2009-01-01

    Objectives To assess the clinical value of ultrasonography (US) and bioelectrical impedance analysis (BIA) in analyzing abdominal fat contents of obese children and adolescents through comparison with MRI. A correlation with other obese related metabolic parameters was conducted. Methods Ninety 7-17-y-old obese children and adolescents (60 boys and 30 girls with mean age of 9.6 ± 2.9 y and mean BMI of 24.5 ± 4.5 kg/m2) were recruited. Metabolic parameters were measured, and insulin resistance was estimated according to homeostasis model assess-ment (HOMA-IR). On the same day abdomen subcutaneous fat thickness (SFTUS) was measured by US. Body fat mass (FMBIA) and abdominal visceral fat area (VFABIA) were analyzed by bioelectrical impedance analysis (BIA). After obtaining informed consent, abdominal MRI was performed in 20 subjects. Each section of umbilicus level was analyzed by image threshold value segmentation using SigmaScan Pro 5 and abdominal subcutaneous fat area (SFAMRI) and visceral fat area (VFAMRI) were calculated. Results (1) A strong positive association was found between SFTUS and SFAMRI (P< 0.05), VFABIA and VFAMRI (P < 0.01) respectively. (2) FMBIA and SFAMRI, VFAMRI, SFTUS also showed significant correlations (P < 0.05). (3) VFAMRI showed extremely significant positive correlations with TG, Insulin,C-peptide and HOMA-IR (P < 0.01 ) ; SFAMRI was also correlated positively with them (P < 0.05). (4) SFTUS was correlated positively with UA (uric acid), Insulin, 2HIns (insulin measured at 2 hours after meal), C-peptide,2HC-peptide (C-peptide measured at 2 hours after meal) and HOMA-IR (P < 0.01). (5) VFABIA was correlated significant positively with UA, insulin, TG, 2HIns and HOMA-IR. FMBIA showed positive correlation with UA, Insulin,2HIns, C-peptide, 2HC-peptide and HOMA-IR. Conclusions abdominal subcutaneous and visceral fat of obese children and adolescents evaluated by US and BIA are correlated well with those assessed by MRI, and also correlated

  13. Association between markers of glucose metabolism and risk of colorectal cancer

    Science.gov (United States)

    Xu, Jinming; Ye, Yao; Wu, Han; Duerksen-Hughes, Penelope; Zhang, Honghe; Li, Peiwei; Huang, Jian; Yang, Jun; Wu, Yihua; Xia, Dajing

    2016-01-01

    Objectives Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach. Design Systematic review and meta-analysis. Data sources PubMed and EMBASE were searched up to May 2015. Primary and secondary outcome measures Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose–response, meta-regression, subgroup and publication bias analyses were conducted. Results 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case–control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer. Conclusions The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for

  14. Impact of Chronic Periodontitis on Levels of Glucoregulatory Biomarkers in Gingival Crevicular Fluid of Adults with and without Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Hasaan G Mohamed

    Full Text Available The relationship between diabetes and periodontal disease is bidirectional, but information about the effect of chronic periodontitis on the levels of the glucoregulatory biomarkers locally in gingival crevicular fluid (GCF is limited. The aim of this study was to compare the levels of 10 glucoregulatory biomarkers in GCF, firstly in subjects with type 2 diabetes (T2DM presenting with and without chronic periodontitis and secondly, in subjects without diabetes, with and without chronic periodontitis. The material comprised a total of 152 subjects, stratified as: 54 with T2DM and chronic periodontitis (G1, 24 with T2DM (G2, 30 with chronic periodontitis (G3 and 44 without T2DM or periodontitis (G4. The levels of the biomarkers were measured using multiplex biometric immunoassays. Periodontal pocket depths were recorded in mm. Subsets G1 and G2 and subsets G3 and G4 were compared independently. Among T2DM subjects, GIP, GLP-1 and glucagon were significantly up-regulated in G1 compared to G2. Moreover, there were no statistical differences between the two groups regarding C-peptide, insulin, ghrelin, leptin and PAI-1. Comparisons among individuals without T2DM revealed significantly lower amounts of C-peptide and ghrelin in G3 than in G4. The number of sites with pocket depth ≥ 4mm correlated negatively with C-peptide (Spearman's correlation co-efficient: -0.240, P < 0.01 and positively with GIP and visfatin (Spearman's correlation co-efficient: 0.255 and 0.241, respectively, P < 0.01. The results demonstrate that chronic periodontitis adversely influences the GCF levels of glucoregulatory biomarkers, as it is associated with disturbed levels of biomarkers related to the onset of T2DM and its medical complications.

  15. Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on type 1 diabetes in NOD model.

    Science.gov (United States)

    Hu, Jianxia; Wang, Yangang; Wang, Fang; Wang, Luan; Yu, Xiaolong; Sun, Ruixia; Wang, Zhongchao; Wang, Li; Gao, Hong; Fu, Zhengju; Zhao, Wenjuan; Yan, Shengli

    2015-02-01

    Type 1 diabetes is an autoimmune disease that results from an inflammatory destruction of β-cells in islets. Mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs) own a peculiar immunomodulatory feature and might reverse the inflammatory destruction and repair the function of β-cells. Sixty NOD mice were divided into four groups, including normal control group, WJ-MSCs prevention group (before onset), WJ-MSCs treatment group (after onset), and diabetic control group. After homologous therapy, onset time of diabetes, levels of fasting plasma glucose (FPG), fed blood glucose and C-peptide, regulation of cytokines, and islet cells were examined and evaluated. After WJ-MSCs infusion, FPG and fed blood glucose in WJ-MSCs treatment group decreased to normal level in 6-8 days and maintained for 6 weeks. Level of fasting C-peptide of these mice was higher compared to diabetic control mice (P=0.027). In WJ-MSCs prevention group, WJ-MSCs played a protective role for 8-week delayed onset of diabetes, and fasting C-peptide in this group was higher compared to the other two diabetic groups (P=0.013, 0.035). Compared with diabetic control group, frequencies of CD4+CD25+Foxp3+ Tregs in WJ-MSCs prevention group and treatment group were higher, while levels of IL-2, IFN-γ, and TNF-α were lower (Pcells no matter before or after onset of T1DM. WJ-MSCs might be an effective method for T1DM.

  16. Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control via different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Otsuka, Yuichiro; Yamaguchi, Suguru; Furukawa, Asami; Kosuda, Minami; Nakazaki, Mitsuhiro; Ishihara, Hisamitsu

    2015-01-01

    This study aimed to explore the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide metformin on the secretion of insulin and glucagon, as well as incretin levels, in Japanese subjects with type 2 diabetes mellitus poorly controlled with insulin monotherapy. This was a single-center, randomized, open-label, parallel group study, enrolling 25 subjects. Eleven patients (hemoglobin A1c [HbA1c] 8.40 ± 0.96%) and 10 patients (8.10 ± 0.54%) on insulin monotherapy completed 12-week treatment with sitagliptin (50 mg) and metformin (750 mg), respectively. Before and after treatment, each subject underwent a meal tolerance test. The plasma glucose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), C-peptide, and glucagon responses to a meal challenge were measured. HbA1c reductions were similar in patients treated with sitagliptin (0.76 ± 0.18%) and metformin (0.77 ± 0.17%). In the sitagliptin group, glucose excursion during a meal tolerance test was reduced and accompanied by elevations in active GLP-1 and active GIP concentrations. C-peptide levels were unaltered despite reduced glucose responses, while glucagon responses were significantly suppressed (-7.93 ± 1.95% of baseline). In the metformin group, glucose excursion and incretin responses were unaltered. C-peptide levels were slightly increased but glucagon responses were unchanged. Our data indicate that sitagliptin and metformin exert different effects on islet hormone secretion in Japanese type 2 diabetic patients on insulin monotherapy. A glucagon suppressing effect of sitagliptin could be one of the factors improving blood glucose control in patients inadequately controlled with insulin therapy. PMID:25328079

  17. A case of low serum insulin levels in a patient with insulinoma

    Science.gov (United States)

    Sun, Ding-Ping

    2016-01-01

    Summary Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Traditionally, inappropriately elevated levels of insulin in the face of hypoglycemia are the key to diagnosis. However, contradictory levels of insulin and C-peptide do not necessarily exclude the diagnosis. A 50-year-old female was brought to our emergency department because of conscious disturbance on the previous night. She had no history of diabetes mellitus, and was not using any medications or alcohol. Laboratory data showed low sugar, a significantly low insulin level, and elevated C-peptide. After admission, she had multiple episodes of spontaneous hypoglycemia after overnight fasts without discomfort. It was considered that a neuroendocrine tumor was the source of her hypoglycemia. CT scan of the abdomen revealed a 1.1cm hypervascular nodule in the pancreatic tail. Elective laparoscopic distal pancreatectomy was incorporated into her treatment course. A 1.2×1.0cm homogenous well-encapsulated tumor was resected. We monitored her glucose levels in the outpatient clinic every month for a period of six months. She did not have another episode of spontaneous hypoglycemia. Learning points Insulinoma causes endogenous hypoglycemia – it cannot be ruled out in patients presenting with hypoglycemia and low insulin levels; history and imaging studies should be done for further assessmentA 24-h fast test has the same clinical significance as that of 72-h fast testC-peptide is a useful biochemical marker in addition to serum insulin, which can be used to diagnose insulinomasCT scan is used to measure the tumor size and localize the tumor. However, definitive diagnosis is only achieved through histopathologic evaluation of diseased tissue PMID:27555915

  18. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Vanelli Maurizio

    2011-03-01

    Full Text Available Abstract Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22 has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c, glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab in children during the first year after diagnosis of type 1 diabetes. Methods The C1858T variant was genotyped in an international cohort of children (n = 257 patients with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03 for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002, which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03. Conclusions The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children.

  19. Ketosis Onset Type 2 Diabetes Had Better Islet β-Cell Function and More Serious Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hongyun Lu

    2014-01-01

    Full Text Available Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM, but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases and nonketotic onset group (78 cases. After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β and insulin resistance (HOMA-IR. Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD than nonketotic group (P=0.04. Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC0–0.5, AUC0–1, AUC0–3 (P<0.05. Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P<0.05. From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

  20. Detection and significance of serum insulin-like growth factor-1 in patients with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis

    Institute of Scientific and Technical Information of China (English)

    Yan-Rong Kang; Pei-Li Gu

    2016-01-01

    Objective:To investigate the content of insulin-like growth factor-1 (IGF-1) in serum and the relationship with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis.Methods:A total of 86 cases of patients with type 2 diabetes, 82 cases of patients with osteoporosis, 79 cases of patients with type 2 diabetic osteoporosis and 86 cases of healthy person were selected, the levels of IGF-1, diabetes related factors (fasting plasma c-peptide, FIN, HbA1c, GLU) and osteoporosis related factors (BMP, osteocalcin,β-CTx, P1NP, lumbar vertebra BMD) were detected, the relationship between the above indicators were compared with those of the disease.Results: In each group, content change of IGF-1 was not statistically significant; content changes of IGF-1, BMP and osteocalcin were control group>type 2 diabetes group>osteoporosis group>type 2 diabetic osteoporosis group. Diabetic osteoporosis enhanced the decrease of IGF-1 content. The contents ofβ-CTx and P1NP in osteoporosis group and diabetic osteoporosis group were similar, which were significantly lower than that in control group and type 2 diabetes group. The level of lumbar vertebra BMD in osteoporosis group and diabetic osteoporosis group were the lowest. Fasting plasma c-peptide in diabetes group and diabetic osteoporosis group were significantly lower than that in control group and osteoporosis group, and the content of fasting plasma c-peptide in diabetic osteoporosis group was the lowest. The contents of FIN, HbA1c and GLU in type 2 diabetes group and type 2 diabetic osteoporosis group were significantly higher than that in control group and osteoporosis group.Conclusion:IGF-1 was related with type 2 diabetes, osteoporosis and type 2 diabetic osteoporosis, and could offer help for predicting type 2 diabetes and osteoporosis in the future.

  1. Beneficial effect of tagatose consumption on postprandial hyperglycemia in Koreans: a double-blind crossover designed study.

    Science.gov (United States)

    Kwak, Jung Hyun; Kim, Min Sun; Lee, Jin Hee; Yang, Yoon Jung; Lee, Ki Ho; Kim, Oh Yoen; Lee, Jong Ho

    2013-08-01

    The present study determined the effect of tagatose supplementation on postprandial hyperglycemia in normal (n = 54) and hyperglycemic subjects [n = 40, impaired fasting glucose (IFG) and newly diagnosed type 2 diabetes]. In a double-blind crossover designed study, study subjects were randomly assigned to consume a sucralose-erythritol drink (the placebo) or a tagatose-containing drink (the test) with a seven-day interval. Finally, 85 subjects completed the study (normal, n = 52; hyperglycemic, n = 33). Blood samples were collected at 0, 30, 60 and 120 min after ingestion and analyzed for fasting and postprandial levels of glucose, insulin and C-peptide. Basic anthropometric parameters and lipid files were also measured. Hyperglycemic subjects were basically older and heavier, and showed higher levels of triglyceride, total- and LDL-cholesterols and apolipoprotein AI and B compared with normal subjects. After consuming the tagatose (5 g)-containing drink, hyperglycemic subjects had a significant reduction in serum levels of glucose at 120 min (p = 0.019) and glucose area under the curve (AUC) (p = 0.017), however these were not observed in normal subjects. When ages were matched between the two groups, the glucose response patterns were shown to be similar. Additionally, normal subjects who received a high-dose of tagatose-containing drinks (10 g) showed significantly lower levels of insulin at 30 min (p = 0.004) and 60 min (p = 0.011), insulin AUC (p = 0.009), and C-peptide at 30 min (p = 0.004), 60 min (p = 0.011) and C-peptide AUC (p = 0.023). In conclusion, a single dietary supplement in the form of a tagatose-containing drink may be beneficial for controlling postprandial glycemic response in Koreans. PMID:23760573

  2. An extract from date seeds stimulates endogenous insulin secretion in streptozotocin-induced type I diabetic rats

    Directory of Open Access Journals (Sweden)

    Ahmed F. El Fouhil

    2013-11-01

    Full Text Available Background: The efficacy of an extract from date seeds has been tested successfully on the glycemic control of type I diabetes mellitus in rats. A suggestion that date seed extract could stimulate certain cells to differentiate into insulin-secreting cells has been proposed. In order to investigate such a possibility, this study was conducted to measure C-peptide levels in the serum of type 1 diabetic rats treated with date seed extract. Methods: Two hundred rats were divided into 4 groups. Group I served as the control. Group II was given daily ingestions of 10 ml of date seed extract. Groups III and IV were made diabetic by streptozotocin injection and were given daily subcutaneous injections of 3 IU/day of insulin for 8 weeks. Group IV received, in addition, daily ingestions of 10 ml of seed extract. At the end of experiment, blood samples were collected from each rat, and blood glucose and serum Cpeptide levels were measured. Results: No significant differences in the means of blood glucose and serum C-peptide levels were observed between groups I (control group and II (date seed extract-treated control group. Group IV (date seed extract-insulin-treated diabetic group showed a statistically significant reduction in the mean blood glucose level compared to Group III (insulin-treated diabetic group. The mean serum C-peptide level was significantly higher in group IV compared to group III. Conclusion: Biochemical results suggested an increase in endogenous insulin secretion in the case of type 1 diabetic rats treated with date seed extract, which might be the cause of its hypoglycemic effect.

  3. Bayesian functional integral method for inferring continuous data from discrete measurements.

    Science.gov (United States)

    Heuett, William J; Miller, Bernard V; Racette, Susan B; Holloszy, John O; Chow, Carson C; Periwal, Vipul

    2012-02-01

    Inference of the insulin secretion rate (ISR) from C-peptide measurements as a quantification of pancreatic β-cell function is clinically important in diseases related to reduced insulin sensitivity and insulin action. ISR derived from C-peptide concentration is an example of nonparametric Bayesian model selection where a proposed ISR time-course is considered to be a "model". An inferred value of inaccessible continuous variables from discrete observable data is often problematic in biology and medicine, because it is a priori unclear how robust the inference is to the deletion of data points, and a closely related question, how much smoothness or continuity the data actually support. Predictions weighted by the posterior distribution can be cast as functional integrals as used in statistical field theory. Functional integrals are generally difficult to evaluate, especially for nonanalytic constraints such as positivity of the estimated parameters. We propose a computationally tractable method that uses the exact solution of an associated likelihood function as a prior probability distribution for a Markov-chain Monte Carlo evaluation of the posterior for the full model. As a concrete application of our method, we calculate the ISR from actual clinical C-peptide measurements in human subjects with varying degrees of insulin sensitivity. Our method demonstrates the feasibility of functional integral Bayesian model selection as a practical method for such data-driven inference, allowing the data to determine the smoothing timescale and the width of the prior probability distribution on the space of models. In particular, our model comparison method determines the discrete time-step for interpolation of the unobservable continuous variable that is supported by the data. Attempts to go to finer discrete time-steps lead to less likely models. PMID:22325261

  4. Severe deterioration of psoriasis due to an insulinoma.

    LENUS (Irish Health Repository)

    Field, S

    2008-03-01

    We report a case of a 56-year-old woman who presented with a severe exacerbation of psoriasis with concurrent hypoglycaemic episodes. Methotrexate 17.5 mg weekly was required to control her psoriasis. Investigation of her hypoglycaemia showed raised levels of insulin, C-peptide and proinsulin. Radiological investigation showed a tumour at the tail of the pancreas and the diagnosis was insulinoma. A spleen-preserving distal pancreatectomy was performed and the hypoglycaemic symptoms resolved. Immediately following the pancreatectomy, methotrexate was stopped and the patient\\'s psoriasis went into remission. During a 2-year follow-up, she has required only minimal topical treatment for her skin.

  5. Early metabolic improvement following bariatric surgery in morbidly obese adolescents.

    Science.gov (United States)

    Teeple, E A; Teich, S; Schuster, D P; Michalsky, M P

    2012-01-01

    Bariatric surgery results in durable weight loss and improved comorbidities. The objectives of this study were to examine the efficacy of gastric bypass in reducing comorbid burden and improving metabolic status among morbidly obese adolescents. The medical records of 15 gastric bypass patients were retrospectively reviewed. Changes in metabolic markers were determined at baseline, 1 and 2 years post-operatively. Comparative analysis demonstrated significant improvement in weight, BMI, insulin, HbA1C, C-peptide, %B, %S, IR, cholesterol, percentile cholesterol, TG, percentile TG, HDL, percentile HDL, LDL, percentile LDL, and VLDL. Results support bariatric surgery as a treatment for morbidly obese adolescents with comorbidities.

  6. Impaired proinsulin secretion before and during oral glucose stimulation in HIV-infected patients who display fat redistribution

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Halsall, Ian;

    2007-01-01

    The beta-cell function of HIV-infected patients on highly active antiretroviral therapy who display lipodystrophy may be impaired. An early defect in beta-cell function may be characterized by an increase in secretion of 32-33 split proinsulin (SP) and intact proinsulin (IP). To address this issue...... SP and IP during the early phase (0, 10, and 20 minutes) and during the late phase (45, 75, and 105 minutes) of the OGTT compared with NONLIPO patients (Ps < .05). LIPO patients exhibited significantly increased fasting SP/IP ratio, fasting SP/insulin ratio, and total proinsulin to C-peptide ratio...

  7. Interactions of the TnaC nascent peptide with rRNA in the exit tunnel enable the ribosome to respond to free tryptophan

    OpenAIRE

    Martínez, Allyson K.; GORDON, EMILY; Sengupta, Arnab; Shirole, Nitin; Klepacki, Dorota; Martinez-Garriga, Blanca; Brown, Lewis M.; Benedik, Michael J.; Yanofsky, Charles; Mankin, Alexander S.; Vazquez-Laslop, Nora; Sachs, Matthew S.; Cruz-Vera, Luis R.

    2013-01-01

    A transcriptional attenuation mechanism regulates expression of the bacterial tnaCAB operon. This mechanism requires ribosomal arrest induced by the regulatory nascent TnaC peptide in response to free L-tryptophan (L-Trp). In this study we demonstrate, using genetic and biochemical analyses, that in Escherichia coli, TnaC residue I19 and 23S rRNA nucleotide A2058 are essential for the ribosome’s ability to sense free L-Trp. We show that the mutational change A2058U in 23S rRNA reduces the con...

  8. Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial.

    Directory of Open Access Journals (Sweden)

    Stephan Martin

    Full Text Available BACKGROUND: Recent evidence suggests that the lipid-lowering agent atorvastatin is also a potent immunomodulator. The aim of this study was to investigate the possible effect of atorvastatin on the decline of residual beta cell function in recent-onset type 1 diabetes. METHODS AND FINDINGS: The randomised placebo-controlled Diabetes and Atorvastatin (DIATOR Trial included 89 patients with newly diagnosed type 1 diabetes and islet autoantibodies (mean age 30 years, 40% females, in 12 centres in Germany. Patients received placebo or 80 mg/d atorvastatin for 18 months. As primary outcome stimulated serum C-peptide levels were determined 90 min after a standardized liquid mixed meal. An intent-to-treat analysis was performed. Fasting and stimulated C-peptide levels were not significantly different between groups at 18 months. However, median fasting serum C-peptide levels dropped from baseline to 12 and 18 months in the placebo group (from 0. 34 to 0.23 and 0.20 nmol/l, p<0.001 versus a nonsignificant decline in the atorvastatin group (from 0.34 to 0.27 and 0.30 nmol/l, ns. Median stimulated C-peptide concentrations declined between baseline and 12 months (placebo from 0.89 to 0.71 nmol/l, atorvastatin from 0.88 to 0.73 nmol/l, p<0.01 each followed by a major loss by month 18 in the placebo group (to 0.48 nmol/l, p = 0.047 but not in the atorvastatin group (to 0.71 nmol/l, ns. Median levels of total cholesterol and C-reactive protein decreased in the atorvastatin group only (p<0.001 and p = 0.04. Metabolic control was similar between groups. CONCLUSIONS: Atorvastatin treatment did not significantly preserve beta cell function although there may have been a slower decline of beta-cell function which merits further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00974740.

  9. Immune intervention in type 1 diabetes

    OpenAIRE

    Michels, Aaron W; Eisenbarth, George S

    2011-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results in the specific immune destruction of insulin producing beta cells. Currently there is no cure for T1D and treatment for the disease consists of lifelong administration of insulin. Immunotherapies aimed at preventing beta cell destruction in T1D patients with residual c-peptide or in individuals developing T1D are being evaluated. Networks of researchers such as TrialNet and the Immune Tolerance Network in the U.S. and similar...

  10. Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolism

    DEFF Research Database (Denmark)

    Hansen, Max; Baunsgaard, D.; Autrup, H.;

    2008-01-01

    We have shown previously that a high sucrose intake increases the background level of somatic mutations and the level of bulky DNA adducts in the colon epithelium of rats. The mechanism may involve either glucose or fructose formed by hydrolysis of sucrose. Male Big Blue (R) rats were fed 30......% sucrose, glucose, fructose or potato starch as part of the diet. Mutation rates and bulky DNA adduct levels were determined in colon and liver. The concentration of short-chain fatty acids and pH were deter-mined in caecum, C-peptide was determined in plasma, biomarkers for oxidative damage...

  11. Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread

    DEFF Research Database (Denmark)

    Juntunen, Katri S; Laaksonen, David E; Autio, Karin;

    2003-01-01

    -fiber rye bread; each bread provided 50 g available carbohydrate and was served with breakfast. Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and serum C-peptide were measured in fasting and 8 postprandial blood samples. In vitro starch hydrolysis...... breads were found. Glucose and glucagon-like peptide 1 responses to the rye breads were not significantly different from those to the control, except at 150 and 180 min. In vitro starch hydrolysis was slower in all rye breads than in the control, and the structure of continuous matrix and starch granules...

  12. Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study

    Directory of Open Access Journals (Sweden)

    Serdar Farhan

    2012-01-01

    Results. Fasting fetuin-A correlated with BMI in women with former GDM (r=0.90, P<0.0001 but showed no association with parameters of glucose tolerance in women with GDM or post-GDM. GDM featured significantly lower insulin sensitivity and higher insulin and C-peptide secretion profiles compared to NGT during pregnancy (P<0.05. Fasting and postprandial fetuin-A did not differ between groups, neither during nor after pregnancy. Conclusion. Fetuin-A is not influenced by glucose tolerance during or after pregnancy or acute glucose elevations following glucose ingestion in young women, but closely relates to BMI early postpartum.

  13. Analysis of proinsulin and its conversion products by reversed-phase high-performance liquid chromatography

    DEFF Research Database (Denmark)

    Linde, S; Welinder, B S; Nielsen, Jens Høiriis

    1993-01-01

    Proinsulin is synthesized in the beta-cells of the endocrine pancreas, one of the four cell types found in the islets of Langerhans. Specific enzymatic cleavage of proinsulin results in the formation of equimolar amounts of insulin and C-peptide, via several intermediate split-proinsulin forms....../or posttranslational processes (enzymatic conversion, intracellular degradation) could be possible explanations. Elevated amounts of proinsulin-immunoreactive material (PIM) have been described to occur in various conditions/diseases, suggesting alterations in beta-cell function, but the composition of the secreted...

  14. Fructans of Jerusalem artichokes

    DEFF Research Database (Denmark)

    Rumessen, J J; Bodé, S; Hamberg, O;

    1990-01-01

    Fructans are naturally occurring plant oligosaccharides with sweetening properties. Fructans (FAs) isolated from Jerusalem artichokes (Helianthus tuberosus) were studied with respect to intestinal handling and influence on blood glucose (BG), insulin, and C-peptide responses in eight healthy...... subjects. The responses were compared with those for fructose ingestion. The effect of FAs added to a wheat-starch meal was also studied. Standardized breath-hydrogen excretion indicated that FAs were completely malabsorbed and, after a 20-g dose, traces of FA were detected in 24-h urine collections in one...

  15. 胰岛素抵抗与2型糖尿病合并脑梗塞的关系%Association between Insulin Resistance and Type 2 Diabetes with Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    陈诗鸿; 刘恩琴; 赵忠红

    2003-01-01

    Objective To investigate the relationship between insulin resistance and type 2 diabetes mellitus with cerebral infarction(CI) .Methods Chinic dataof fasting insulin level(FINS) ,C - peptide (CP) ,fasting plasma glucose (FPG)and insulin - sensitivity index (ISI) were determined in 56 CI and 31 normal controls (NC). Result The levels of FINS, CP and FPG etc.in CI were higher than those in NC(P< 0.01).Conclusion There are obvious IR and hyperinsulinemia in the type 2 diabetes with CI. These results suggested that reducing of IR might be lowering the incidence of CI in type 2 diabetes.

  16. Association between Type 2 Diabetes with Cerebral Infarction and Insulin Resistance%2型糖尿病并脑梗塞患者胰岛素抵抗的临床分析

    Institute of Scientific and Technical Information of China (English)

    刘恩琴; 陈诗鸿

    2003-01-01

    Objective To investigate the relationship between insulin resistance and type 2 diabetes mellitus withcerebral infarction (CI). Methods Clinic data of fasting insulin level(FINS), C- peptide (CP), fasting plasma glucose(FPG) and insulin- sensitivity index(ISI) were determined in 56 CI and 31 normal controls (NC). Results The levels ofFINS, CP and FPG etc. in CI were higher than those in NC (P < 0.01 ). Conclusion There are obvious IR andhyperinsulinemia in the type 2 diabetes with CI.These results suggested that reducing of IR might be lowering the incidence ofCI in type 2 diabetes.

  17. Intact proinsulin and beta-cell function in lean and obese subjects with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Røder, M E; Dinesen, B; Hartling, S G;

    1999-01-01

    , total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2...... hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease....

  18. Risk of Celiac Disease Autoimmunity is Modified by Non-HLA Genetic Markers During the First Year of Clinical Type 1 Diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H.; Hansen, Dorthe; Mortensen, Henrik B.;

    2014-01-01

    Aims: This study plotted the prevalence of celiac disease associated antibodies in relation to demographic patterns, genetic and metabolic markers during the first year after diagnosis in a multinational cohort of children with T1D. Material and Methods: Sera from a total of 261 children (128 males...... measuring IgG-tTG. Children positive in both assays in two consecutive samples were defined as having celiac disease autoimmunity (CDA). Associations between CDA and genotypes of HLA, IL18 rap, CCR 5, PTPN2 and correlations with islet autoantibodies (ICA, GADA, IA2 and IA) and HbA1C and C-peptide were...

  19. 糖尿病性浮腫性硬化症の一例

    OpenAIRE

    宮崎, 睦子; 田口, 昭彦; 櫻木, 志津; 篠原, 健次; 井上, 康

    2003-01-01

    A 66-year-old male complained of thickening of the skin at the face, posterior neck and back after a febrile episode. The patient had obesity, elevated levels of HbA1C and urinary C-peptide. The seological tests for collagen diseases were negative. The serum level of vascular endothelial growth factor (VEGF) was elevated. The biopsied skin specimen revealed the thickening of the dermis by the increased proliferation of collagen fibers, thickening of collagen bundles with fenestrations and inf...

  20. Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

    DEFF Research Database (Denmark)

    Meier, J J; Gethmann, A; Götze, O;

    2006-01-01

    . Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA. RESULTS: GLP-1 administration lowered fasting and postprandial glycaemia (p... administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33+/-0.14 mmol/l in the placebo experiments (ptriglyceride levels was completely...... abolished by GLP-1 (change in triglycerides, -0.023+/-0.045 mmol/l; p

  1. Association of fasting glucagon and proinsulin concentrations with insulin resistance

    DEFF Research Database (Denmark)

    Ferrannini, E; Muscelli, E; Natali, A;

    2007-01-01

    AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic......, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin...

  2. Biosynthesis and periplasmic segregation of human proinsulin in Escherichia coli.

    OpenAIRE

    Chan, S J; J. Weiss; Konrad, M; White, T; Bahl, C; Yu, S D; D. Marks; Steiner, D F

    1981-01-01

    A plasmid containing human preproinsulin cDNA inserted into the endonuclease Pst I site of the ampicillinase gene of plasmid pBR322 was modified by excision of large portions of the ampicillinase-coding region to produce a variety of gene fusion combinations, many of which generated proteins detectable with antisera to insulin or human C peptide. In one case a perfect hybrid of the NH2-terminal half of the leader sequence of ampicillinase (residues -23 to -12) with the human preproinsulin pre...

  3. A Prospective, Multicentre, Open-Label Single-Arm Exploratory Study to Evaluate Efficacy and Safety of Saroglitazar on Hypertriglyceridemia in HIV Associated Lipodystrophy.

    Directory of Open Access Journals (Sweden)

    Alka Deshpande

    Full Text Available This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy.During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG levels from baseline to Week 6 and Week 12. The secondary efficacy endpoints were assessment of low-density-lipoprotein (LDL, very-low-density-lipoprotein (VLDL, high-density-lipoprotein (HDL, non-HDL cholesterol, total cholesterol, apo-lipoprotein (Apo A1, Apo B, and C-peptide and fasting insulin for HOMA beta and HOMA IR. Safety assessment was performed during the study.Saroglitazar 4 mg significantly decreased the serum TG levels from baseline at Week 6 (percent change: -40.98; 95% CI: -50.82, -31.15 and Week 12 (percent change -45.11; 95% CI: -52.37, -37.86. Reduction in VLDL cholesterol (percent change: -46.33; 95% CI: -52.89, -39.76 and total cholesterol (percent change: 7.37; 95% CI: 1.96, 12.78 was observed at week 12 from baseline. Saroglitazar increased HDL cholesterol (percent change: 34.56, 95% CI: 22.22, 46.90, Apo A1 (percent change: 33.16; 95% CI: 18.69, 47.63 and Apo B (percent change: 10.55, 95% CI: 2.86, 18.25 levels at week 12 from baseline. Saroglitazar treatment led to increase in the C-peptide (percent change: 59.42, 95% CI: 48.78, 70.06, fasting insulin levels (percent change: 47.10; 95% CI: 38.63, 55.57, HOMA of beta cell function for C-peptide (percent change: 71.67; 95% CI: 39.09, 104.26 and HOMA of insulin resistance for C-peptide (percent change: 58.29, 95% CI: 46.74, 69.83 at week 12 from baseline. Saroglitazar treatment was safe and well tolerated in this study.Overall, the observed changes in lipid profile after 12 weeks of saroglitazar treatment were in the direction of improvement in patients with HIV

  4. Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3

    OpenAIRE

    Zhu, Xiaorong; ORCI, LELIO; Carroll, Raymond; Norrbom, Christina; Ravazzola, Mariella; Steiner, Donald F.

    2002-01-01

    The neuroendocrine processing endoproteases PC2 and PC1/3 are expressed in the β cells of the islets of Langerhans and participate in the processing of proinsulin to insulin and C-peptide. We have previously shown that disruption of PC2 (SPC2) expression significantly impairs proinsulin processing. Here we report that disruption of the expression of PC1/3 (SPC3) produces a much more severe block in proinsulin conversion. In nulls, pancreatic and circulating proinsulin-like components comprise...

  5. Misfolded Proinsulin Affects Bystander Proinsulin in Neonatal Diabetes*

    OpenAIRE

    Hodish, Israel; Liu, Ming; Rajpal, Gautam; Larkin, Dennis; Holz, Ronald W.; Adams, Aaron; Liu, Leanza; Arvan, Peter

    2009-01-01

    It has previously been shown that misfolded mutant Akita proinsulin in the endoplasmic reticulum engages directly in protein complexes either with nonmutant proinsulin or with “hProCpepGFP” (human proinsulin bearing emerald-GFP within the C-peptide), impairing the trafficking of these “bystander” proinsulin molecules (Liu, M., Hodish, I., Rhodes, C. J., and Arvan, P. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 15841–15846). Herein, we generated transgenic mice, which, in addition to expressing ...

  6. Transient B-Cell Depletion with Anti-CD20 in Combination with Proinsulin DNA Vaccine or Oral Insulin: Immunologic Effects and Efficacy in NOD Mice

    OpenAIRE

    Ghanashyam Sarikonda; Sowbarnika Sachithanantham; Yulia Manenkova; Tinalyn Kupfer; Amanda Posgai; Clive Wasserfall; Philip Bernstein; Laura Straub; Pagni, Philippe P.; Darius Schneider; Teresa Rodriguez Calvo; Marilyne Coulombe; Kevan Herold; Gill, Ronald G.; Mark Atkinson

    2013-01-01

    A recent type 1 diabetes (T1D) clinical trial of rituximab (a B cell-depleting anti-CD20 antibody) achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin) with anti-CD3 antibody (a T cell-directed immunomodulator) offers better protection than either entity alone, indicating that novel combination therapies that i...

  7. A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto).

    OpenAIRE

    Yano, H; Kitano, N; Morimoto, M.; Polonsky, K S; Imura, H; Seino, Y.

    1992-01-01

    We have identified a 65-yr-old nonobese Japanese man with diabetes mellitus, fasting hyperinsulinemia (150-300 pM), and a reduced fasting C-peptide/insulin molar ratio of 2.5-3.0. Fasting hyperinsulinemia was also found in his son and daughter. Analysis of insulin isolated from the serum of the proband and his son by reverse-phase high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials. The insulin gene of the pat...

  8. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans

    DEFF Research Database (Denmark)

    Kjær, Michael; Mikines, K J; Christensen, N J;

    1984-01-01

    Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was ...... of heart rate, free fatty acid, and glycerol was faster. Responses of norepinephrine, cortisol, C-peptide, and lactate were similar in the two groups. Training radically changes hormonal responses but not glucose kinetics in insulin hypoglycemia....

  9. A Bayesian approach to estimating the prehepatic insulin secretion rate

    DEFF Research Database (Denmark)

    Andersen, Kim Emil; Højbjerre, Malene

    the time courses of insulin and C-peptide subsequently are used as known forcing functions. In this work we adopt a Bayesian graphical model to describe the unied model simultaneously. We develop a model that also accounts for both measurement error and process variability. The parameters are estimated...... by a Bayesian approach where efficient posterior sampling is made available through the use of Markov chain Monte Carlo methods. Hereby the ill-posed estimation problem inherited in the coupled differential equation model is regularized by the use of prior knowledge. The method is demonstrated on experimental...

  10. Diurnal changes of biochemical metabolic markers in healthy young males

    DEFF Research Database (Denmark)

    Sennels, Henriette P; Jørgensen, Henrik L; Fahrenkrug, Jan

    2015-01-01

    .06 mmol/L) did not show significant oscillations. CONCLUSIONS: When diagnosing and monitoring metabolic disorders compensation for the 24-h variation of the biochemical metabolic markers is needed especially C-peptide, triglyceride and glucose. Furthermore, the stable HbA1c level through 24 h makes......BACKGROUND: To examine whether time of the day has an effect on the circulating levels of metabolism parameters. METHODS: Venous blood samples were obtained under standardized conditions from 24 healthy young men every third hour through 24 hours. The metabolic markers and melatonin were examined...

  11. Correlations between insulin sensitivity and bone mineral density in non-diabetic men

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Rohold, A; Henriksen, J E;

    2000-01-01

    AIMS: To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hyperglycaemia [corrected] leads to decreased osteoblast proliferation and a negative calcium balance and that insulin...... sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test. RESULTS: Insulin and C-peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0...

  12. Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion

    DEFF Research Database (Denmark)

    Hagemann, Dirk; Holst, Jens Juul; Gethmann, Arnica;

    2007-01-01

    INTRODUCTION: Ghrelin is an orexigenic peptide predominantly secreted by the stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline afterwards, but the mechanisms controlling ghrelin secretion are largely unknown. Since meal ingestion also elicits the secretion...... ghrelin levels 150 and 360 min after meal ingestion (plevels of insulin and C-peptide. CONCLUSIONS: GLP-1 reduces the rise in ghrelin levels in the late...... postprandial period at supraphysiological plasma levels. Most likely, these effects are indirectly mediated through its insulinotropic action. The GLP-1-induced suppression of ghrelin secretion might be involved in its anorexic effects....

  13. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Goetze, Oliver; Anstipp, Jens;

    2004-01-01

    . Gastric emptying was calculated from the (13)CO(2) exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA...... and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 +/- 15 pmol/l for total and 34 +/- 4 pmol/l for intact GIP (P

  14. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial

    DEFF Research Database (Denmark)

    Madsbad, Sten; Schmitz, Ole; Ranstam, Jonas;

    2004-01-01

    .45, 0.60, or 0.75 mg), placebo, or open-label sulfonylurea (glimepiride, 1-4 mg). The primary end point was HbA(1c) after 12 weeks; secondary end points were fasting serum glucose, fasting C-peptide, fasting glucagon, fasting insulin, beta-cell function, body weight, adverse events, and hypoglycemic....... Patients treated with glimepiride had decreased HbA(1c) and fasting glucose, but slightly increased body weight. No safety issues were raised for liraglutide; observed adverse events were mild and transient. CONCLUSIONS: A once-daily dose of liraglutide provides efficacious glycemic control...

  15. Korean Red Ginseng Improves Glucose Control in Subjects with Impaired Fasting Glucose, Impaired Glucose Tolerance, or Newly Diagnosed Type 2 Diabetes Mellitus

    OpenAIRE

    Bang, Hyangju; Kwak, Jung Hyun; Ahn, Hyeon Yeong; Shin, Dong Yeob; Lee, Jong Ho

    2014-01-01

    This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2...

  16. Influence of glycorazmulin on the parameters of carbohydrate metabolism in alloxane diabetes

    Directory of Open Access Journals (Sweden)

    Ziyoda Fayzieva

    2010-09-01

    Full Text Available There was studied effect of glycorazmulin on the morphological structure of the liver and pancreatic gland under the conditions of alloxane diabetes. The study found that that glycorazmulin eliminates pathomorphological changes that occur in alloxane diabetes in the liver and pancreatic gland, and stimulates reparative processes in these organs. The effect of this preparation is mainly directed to stimulation of the regeneration of β-cells. The elimination of histostructural changes resulted in compensation of the damaged metabolic processes in diabetes mellitus. Besides, marked increase in C-peptide in the blood is the confirmation of the insulin secretion stimulation under the effect of this preparation.

  17. Effects of ORP150 on appearance and function of pancreatic beta cells following acute necrotizing pancreatitis.

    Science.gov (United States)

    Deng, Wen-Hong; Chen, Chen; Wang, Wei-Xing; Yu, Jia; Li, Jin-You; Liu, Lei

    2011-06-15

    Pancreatic beta cells produce and release insulin, which decreases the blood glucose level. Endoplasmic reticulum stress caused pancreatic beta cell dysfunction and death in acute necrotizing pancreatitis (ANP). The 150kD oxygen-regulated protein (ORP150) took part in the process of endoplasmic reticulum stress. This study investigated the effect of ORP150 on appearance and function of pancreatic beta cells in ANP. Acute necrotizing pancreatitis relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. The severity of ANP was estimated by serum amylase, secretory phospholipase A(2,) and pancreatic histopathology. The changes in appearance and function of pancreatic beta cells were detected by light and electron microscopy and the levels of serum glucose, insulin, and C-peptide. ORP150 expression was studied using western blot and immunohistochemisty assay. The expression of ORP150 mainly appeared on pancreatic beta cells and decreased gradually during the pathogenesis of ANP. The results of light and electron microscopy indicated pancreatic beta cell dysfunction and death, concomitant with elevation of serum glucose, insulin, and C-peptide in ANP. These results imply a probable role of ORP150 in the changes in appearance and function of pancreatic beta cells following acute necrotizing pancreatitis, through the pathway of endoplasmic reticulum stress.

  18. Linear antigenic mapping of flagellin (FliC) from Salmonella enterica serovar Enteritidis with yeast surface expression system.

    Science.gov (United States)

    Wang, Gaoling; Shi, Bingtian; Li, Tao; Zuo, Teng; Wang, Bin; Si, Wei; Xin, Jiuqing; Yang, Kongbin; Shi, Xuanlin; Liu, Siguo; Liu, Henggui

    2016-02-29

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major cause of food-borne illness around the world and can have significant health implications in humans, poultry and other animals. Flagellin (FliC) is the primary component of bacterial flagella. It has been shown that the FliC of S. Enteritidis is a significant antigenic structure and can elicit strong humoral responses against S. Enteritidis infection in chickens. Here, we constructed a FliC antigen library using a yeast surface expression system. Yeast cells expressing FliC peptide antigens were labeled with chicken sera against S. Enteritidis and sorted using FACS. The analyses of FliC peptides revealed that the FliC linear antigenicity in chickens resided on three domains which were able to elicit strong humoral responses in vivo. Animal experiments further revealed that the antibodies elicited by these antigenic domains were able to significantly inhibit the invasion of S. Enteritidis into the liver and spleen of chickens. These findings will facilitate our better understanding of the humoral responses elicited by FliC in chickens upon infection by S. Enteritidis.

  19. The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex

    Energy Technology Data Exchange (ETDEWEB)

    Thompson,J.; Ryan, Z.; Salisbury, J.; Kumar, R.

    2006-01-01

    Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered {alpha}-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an {alpha}-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.

  20. The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex

    International Nuclear Information System (INIS)

    Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered α-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an α-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin

  1. Effects of EDTA and Sodium Citrate on hormone measurements by fluorometric (FIA and immunofluorometric (IFMA methods

    Directory of Open Access Journals (Sweden)

    Lando Valeria

    2002-05-01

    Full Text Available Abstract Background Measurements of hormonal concentrations by immunoassays using fluorescent tracer substance (Eu3+ are susceptible to the action of chemical agents that may cause alterations in its original structure. Our goal was to verify the effect of two types of anticoagulants in the hormone assays performed by fluorometric (FIA or immunofluorometric (IFMA methods. Methods Blood samples were obtained from 30 outpatients and were drawn in EDTA, sodium citrate, and serum separation Vacutainer®Blood Collection Tubes. Samples were analyzed in automatized equipment AutoDelfia™ (Perkin Elmer Brazil, Wallac, Finland for the following hormones: Luteinizing hormone (LH, Follicle stimulating homone (FSH, prolactin (PRL, growth hormone (GH, Sex hormone binding globulin (SHBG, thyroid stimulating hormone (TSH, insulin, C peptide, total T3, total T4, free T4, estradiol, progesterone, testosterone, and cortisol. Statistical analysis was carried out by Kruskal-Wallis method and Dunn's test. Results No significant differences were seen between samples for LH, FSH, PRL and free T4. Results from GH, TSH, insulin, C peptide, SHBG, total T3, total T4, estradiol, testosterone, cortisol, and progesterone were significant different between serum and EDTA-treated samples groups. Differences were also identified between serum and sodium citrate-treated samples in the analysis for TSH, insulin, total T3, estradiol, testosterone and progesterone. Conclusions We conclude that the hormonal analysis carried through by FIA or IFMA are susceptible to the effects of anticoagulants in the biological material collected that vary depending on the type of assay.

  2. Effect of single physical exercise at 35% VO2 max. intensity on secretion activity of pancreas β-cells and 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus

    International Nuclear Information System (INIS)

    In this report we showed research results of effect of single physical exercise on cycloergometer at 35% VO2 max. intensity on 125J-insulin binding and degradation ability by erythrocyte receptors in children with diabetes mellitus, secreting and non-secreting endogenous insulin. Insulin secretion was evaluated by measurement of C-peptide by Biodet test (Serono) of sensitivity threshold at 0.3 μg/ml. We indicated in children non-secreting endogenous insulin (n=32) there is statistically essential lower 125J-insulin binding with erythrocyte receptor in comparison to children group with C-peptide. Physical exercise on cycloergometer at 35% VO2 max. intensity caused different reaction in range of physiological indices, like acid-base parameters, level of glucose and 125J-insulin binding and degradation. In children devoid of endogenous insulin we indicated statistically nonessential changes in 125J-insulin degradation by non-impaired erythrocytes and by hemolizate, as well. 125J-insulin binding after physical exercise increased in both groups, though change amplitude was different. Obtained research results allowed us to conclude, in children with I-type diabetes, that in dependence of impairment degree of pancreas βcells sensitivity of insulin receptor and/or number of receptors on erythrocyte surface is different

  3. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højberg, P V; Vilsbøll, T; Rabøl, R;

    2008-01-01

    )). CONCLUSIONS: Near-normalisation of blood glucose for 4 weeks improves beta cell responsiveness to both GLP-1 and GIP by a factor of three to four. No effect was found on beta cell responsiveness to glucose alone. CLINICALTRIALS.GOV ID NO.: NCT 00612950. FUNDING: This study was supported by The Novo Nordisk......OBJECTIVE: The incretin effect is attenuated in patients with type 2 diabetes mellitus, partly as a result of impaired beta cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The aim of the present study was to investigate whether 4 weeks......-peptide curve. RESULTS: Before and after near-normalisation of blood glucose, the C-peptide responses did not differ during the early phase of insulin secretion (0-10 min). The late phase C-peptide response (10-120 min) increased during GIP infusion from 33.0 +/- 8.5 to 103.9 +/- 24.2 (nmol/l) x (110 min)(-1...

  4. Application of Allotransplantation of Fetal Liver-derived Stem-Cells for Treatment of Type 1 Diabetes: a Single-arm, Phase 3 Clini¬cal Trial

    Directory of Open Access Journals (Sweden)

    Ali TOOTEE

    2015-10-01

    Full Text Available Background: Stem-cell technology has been advocated as a potentially curative option for treatment of both type 1 and type 2 diabetes. In the current study, we aimed to assess the effectiveness of allotransplantation of fetal liver-derived cells for treatment of patients with type 1 diabetes.Methods: For the purpose of the current study, 72 patients with recently diagnosed type 1 DM were recruited and fetal liver-derived cell suspension was administered by the means of intravenous injection. Anthropometric measurements and clinical data such as body mass index, duration of the disease, daily insulin requirement were recorded as well as some of laboratory indicators of favorable therapeutic response (hemoglobin A1c, c-peptide before and after the intention at 0, 1, 3, 6 and 12 months following the intervention.Results: Administration of fetal liver-derived fetal stem-cells resulted in significant changes in indicators of diabetes control in the patients. Required daily insulin dose and HbA1c showed significant changes, and c-peptide levels decreased significantly during the first three months of follow up period (P= 0.000 although they started the decrease after that point.Conclusion: Stem-cell therapy resulted in significant changes in indicators of diabetes control and beta-cell function. More studies are required to demonstrate effectiveness of stem-cell therapy for type 1 diabetes.  Keywords: Stem cell, Type 1 diabetes, Therapy, Iran 

  5. Stem cell therapy for type 1 diabetes mellitus: a review of recent clinical trials.

    Science.gov (United States)

    Couri, Carlos Eduardo Barra; Voltarelli, Júlio César

    2009-01-01

    Stem cell therapy is one of the most promising treatments for the near future. It is expected that this kind of therapy can ameliorate or even reverse some diseases. With regard to type 1 diabetes, studies analyzing the therapeutic effects of stem cells in humans began in 2003 in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto - SP USP, Brazil, and since then other centers in different countries started to randomize patients in their clinical trials. Herein we summarize recent data about beta cell regeneration, different ways of immune intervention and what is being employed in type 1 diabetic patients with regard to stem cell repertoire to promote regeneration and/or preservation of beta cell mass.The Diabetes Control and Complications Trial (DCCT) was a 7-year longitudinal study that demonstrated the importance of the intensive insulin therapy when compared to conventional treatment in the development of chronic complications in patients with type 1 diabetes mellitus (T1DM). This study also demonstrated another important issue: there is a reverse relationship between C-peptide levels (endogenous indicator of insulin secretion) chronic complications - that is, the higher the C-peptide levels, the lower the incidence of nephropathy, retinopathy and hypoglycemia. From such data, beta cell preservation has become an additional target in the management of T1DM 1.

  6. Murder by insulin: suspected, purported and proven-a review.

    Science.gov (United States)

    Marks, Vincent

    2009-04-01

    Murder by insulin-whether attempted, suspected or proven-is rare. Only 66 cases worldwide could be found for this review. A conviction was secured in 31 cases and additional weapon was employed in 11. Differentiation of attempted homicide from Munchausen syndrome by proxy in the young and from 'mercy killing' in the elderly was not attempted. Most perpetrators were close relatives and most victims were alive when discovered and responded to treatment. Hypoglycaemia is the first clue to homicidal insulin use in living subjects and requires the demonstration of a plasma insulin concentration of generally more than 1000 pmol/L and undetectable plasma C-peptide concentration to establish the diagnosis. Serum glucose measurements are valueless in victims found dead. The presence near the body of insulin vials, syringes or needles, loose talk by the suspected perpetrator or their ready access to insulin may be the only clue. The demonstration of insulin in tissue around an injection site by immunohistopathology or by measuring it in an extract clinches the diagnosis. Immunoassays suitable for clinical use to detect and measure insulin and C-peptide are subject to random errors and cannot be relied upon unless special precautions including separation by gel filtration or HPLC are undertaken prior to analysis. They do not detect or measure accurately a new generation of synthetic insulin analogues. Mass spectrometry will be required to do this and to validate clinical immunoassays, upon which convictions have always had to rely in the past. PMID:20355194

  7. Identification of differential responses to an oral glucose tolerance test in healthy adults.

    Directory of Open Access Journals (Sweden)

    Ciara Morris

    Full Text Available BACKGROUND: In recent years an individual's ability to respond to an acute dietary challenge has emerged as a measure of their biological flexibility. Analysis of such responses has been proposed to be an indicator of health status. However, for this to be fully realised further work on differential responses to nutritional challenge is needed. This study examined whether metabolic phenotyping could identify differential responders to an oral glucose tolerance test (OGTT and examined the phenotypic basis of the response. METHODS AND RESULTS: A total of 214 individuals were recruited and underwent challenge tests in the form of an OGTT and an oral lipid tolerance test (OLTT. Detailed biochemical parameters, body composition and fitness tests were recorded. Mixed model clustering was employed to define 4 metabotypes consisting of 4 different responses to an OGTT. Cluster 1 was of particular interest, with this metabotype having the highest BMI, triacylglycerol, hsCRP, c-peptide, insulin and HOMA- IR score and lowest VO2max. Cluster 1 had a reduced beta cell function and a differential response to insulin and c-peptide during an OGTT. Additionally, cluster 1 displayed a differential response to the OLTT. CONCLUSIONS: This work demonstrated that there were four distinct metabolic responses to the OGTT. Classification of subjects based on their response curves revealed an "at risk" metabolic phenotype.

  8. Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise.

    Science.gov (United States)

    Kim, Min Sun; Goo, Jun Seo; Kim, Ji Eun; Nam, So Hee; Choi, Sun Il; Lee, Hye Ryun; Hwang, In Sik; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Bae, Chang Joon; Cho, Jung Sik; Cho, Jun Yong; Hwang, Dae Youn

    2011-03-01

    Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

  9. Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass.

    Science.gov (United States)

    Baidal, D A; Ricordi, C; Garcia-Contreras, M; Sonnino, A; Fabbri, A

    2016-07-01

    Several studies have evaluated the role of inflammation in type 1 diabetes (T1D). The safety profile and anti-inflammatory properties of high dose omega-3 fatty acids combined with Vitamin D supplementation make this therapy a possible candidate for T1D intervention trials. Herein, we describe the case of a 14-year-old boy with new onset T1D treated with high dose Omega-3 and vitamin D3. By 12 months, peak C-peptide increased to 0.55 nmol/L (1.66 ng/mL) corresponding to a 20% increment from baseline and AUC C-peptide was slightly higher compared to 9 months (0.33 vs. 0.30 nmol/L/min) although remaining slightly lower than baseline. Combination high-dose Omega-3 fatty acids and high-dose vitamin D3 therapy was well tolerated and may have beneficial effects on beta-cell function. Randomized controlled trials could be of assistance to determine whether this therapy may result in the preservation of beta-cell function in patients with new onset T1D.

  10. Differentiation of Human Mesenchymal Stem Cells into Insulin Producing Cells by Using A Lentiviral Vector Carrying PDX1

    Directory of Open Access Journals (Sweden)

    Amir Allahverdi

    2015-07-01

    Full Text Available Objective: Type I diabetes is an immunologically-mediated devastation of insulin producing cells (IPCs in the pancreatic islet. Stem cells that produce β-cells are a new promising tool. Adult stem cells such as mesenchymal stem cells (MSCs are self renewing multi potent cells showing capabilities to differentiate into ectodermal, mesodermal and endodermal tissues. Pancreatic and duodenal homeobox factor 1 (PDX1 is a master regulator gene required for embryonic development of the pancreas and is crucial for normal pancreatic islets activities in adults. Materials and Methods: We induced the over-expression of the PDX1 gene in human bone marrow MSCs (BM-MSCs by Lenti-PDX1 in order to generate IPCs. Next, we examine the ability of the cells by measuring insulin/c-peptide production and INSULIN and PDX1 gene expressions. Results: After transduction, MSCs changed their morphology at day 5 and gradually differentiated into IPCs. INSULIN and PDX1 expressions were confirmed by real time polymerase chain reaction (RT-PCR and immunostaining. IPC secreted insulin and C-peptide in the media that contained different glucose concentrations. Conclusion: MSCs differentiated into IPCs by genetic manipulation. Our result showed that lentiviral vectors could deliver PDX1 gene to MSCs and induce pancreatic differentiation.

  11. Hypoglycaemic activity of Bixa orellana extract in the dog.

    Science.gov (United States)

    Russell, K R M; Omoruyi, F O; Pascoe, K O; Morrison, E Y St A

    2008-05-01

    In West Indian folklore, a variety of plants are used for medicinal purposes. One such plant, Bixa orellana (annatto), is commonly used in the treatment of diabetes mellitus. Preliminary studies have shown that a crude annatto seed extract exhibited either glucose lowering or hyperglycaemia-inducing activity depending on how it was further manipulated. This present investigation sought to determine the effects of the glucose-lowering extract on C-peptide and streptozotocin-induced diabetic dogs. This annatto extract was found to decrease blood glucose levels in fasting normoglycaemic and streptozotocin-induced diabetic dogs. In addition, in normal dogs, it suppressed the postprandial rise in blood glucose after an oral glucose load. Interestingly, the extract also caused an increase in insulin-to-glucose ratio in normal dogs. Increased insulin levels were not due to increased insulin synthesis as after 1-h residence time and half-hour postprandial, decreased C-peptide levels was observed. It was concluded that Bixa orellana (annatto) lowered blood glucose by stimulating peripheral utilization of glucose, and it is possible that this glucose-lowering extract might be of pharmacological importance. PMID:18773125

  12. [Analysis of possible causes activation a stomach and pancreas excretory and incretory function after completion of space flight on the international space station].

    Science.gov (United States)

    Afonin, B V

    2013-01-01

    The research excretory and incretory of activity of a stomach and pancreas is carried out at astronauts in the early period after completion of space flights of various duration. It is shown, that the increase of the contents of gastric and pancreatic enzymes and hormones (insulin and C-peptide) in blood reflects increased excretory and incretory activity of organs of gastroduodenal area which arises in weightlessness. The complex of countermeasures, which prevent ingress of subjects, infected by Helicobacter pylori in space flight crew, excluded participation of this microorganism in the mechanism of increase of secretory activity of a stomach. The absence of interrelation between increase of secretory activity of gastroduodenal area organs and space flights' duration has allowed to exclude the hypokinetic mechanism which determined by duration of stay in weightlessness. It was shown that after the end of space flights the increase ofbasal excretory activity of organs of gastroduodenal area occurs simultaneously with increase of a fasting insulin secretion. The changes in gastroduodenal area organs revealed after space flights were are compared to similar changes received in ground-based experiments, simulating hemodynamic reorganization in venous system of abdominal cavity, arising in weightlessness. The conclusion is made, that the basic mechanism of changes of a functional condition of digestive system in space flights, is determined by reorganization venous hemodynamic in abdominal cavity organs reproduced in ground experiments. Increase insulin and C-peptide after space flights are considered as hormonal component of this hemodynamic mechanism.

  13. Stem cell therapy for type 1 diabetes mellitus: a review of recent clinical trials

    Directory of Open Access Journals (Sweden)

    Couri Carlos

    2009-10-01

    Full Text Available Abstract Stem cell therapy is one of the most promising treatments for the near future. It is expected that this kind of therapy can ameliorate or even reverse some diseases. With regard to type 1 diabetes, studies analyzing the therapeutic effects of stem cells in humans began in 2003 in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto - SP USP, Brazil, and since then other centers in different countries started to randomize patients in their clinical trials. Herein we summarize recent data about beta cell regeneration, different ways of immune intervention and what is being employed in type 1 diabetic patients with regard to stem cell repertoire to promote regeneration and/or preservation of beta cell mass. The Diabetes Control and Complications Trial (DCCT was a 7-year longitudinal study that demonstrated the importance of the intensive insulin therapy when compared to conventional treatment in the development of chronic complications in patients with type 1 diabetes mellitus (T1DM. This study also demonstrated another important issue: there is a reverse relationship between C-peptide levels (endogenous indicator of insulin secretion chronic complications - that is, the higher the C-peptide levels, the lower the incidence of nephropathy, retinopathy and hypoglycemia. From such data, beta cell preservation has become an additional target in the management of T1DM 1.

  14. Serum resistin and adiponectin concentrations in patients with overweight and obesity

    Institute of Scientific and Technical Information of China (English)

    LUO Rong; LI Xiao-ping; ZHAO Yan

    2007-01-01

    Objective:To explore the serum levels of resistin and adiponectin in patients with overweight and obesity. Methods: Fifty-eight cases with normal weight and 24 patients with overweight and obesity have taken fasting blood samples for measurements of plasma glucose, plasma lipids, insulin, C-peptide,thyroid hormones, C-response protein, interleukin-6, TNF-α, leptin, adiponectin and resistin. Results:The concentrations of resistin in cases with overweight and obesity were significant higher than those in the normal weight cases (16.01± 8. 60 vs 11. 63+ 9. 05 ng/ml, P = 0. 047). Pearson relation analysis showed that serum resistin concentrations were positively correlated with age (r= 0. 476, P= 0. 019), but negatively correlated with C-peptide (r=- 0.45, P = 0. 024), and adiponectin concentrations were positively correlated with HDL-c (r=0. 463, P=0. 023) and systolic blood pressure (r=0. 409, P=0. 047) in overweight and obesity cases. Conclusion: The concentrations of resistin in cases with over-weight and obesity are higher, and there is no correlation between resistin and blood glucose, blood lipids and insulin,while the serum adiponectin concentrations positively correlated with HDL-c and systolic blood pressure.

  15. Human fetal islet transplantation in type 1 diabetic patients: comparison of metabolic effects between single and multiple implantation regimens.

    Science.gov (United States)

    Djordjevic, P B; Lalic, N M; Jotic, A; Paunovic, I; Lalic, K; Raketic, N; Nikolic, D; Zamaklar, M; Rajkovic, N; Lukic, L; Dimitrijevic-Sreckovic, V; Dragasevic, M; Nikolic, D; Markovic, I

    2004-11-01

    Previous studies suggest that multiple transplantations might be equally efficient to a single regimen for human adult islets. The aim of this study was to compare metabolic parameters after each of the two regimens of human fetal islet (HFI) transplantation in type 1 diabetics. In group A (single transplant, n = 9), 180 +/- 20 x 1000 HFI equivalents (IEQs) were implanted by a single IM injection; in group B (multiple transplants, n = 8) islets were implanted as three consecutive injections (60 +/- 10 x 1000 IEQs) at 7-day intervals. We analyzed the metabolic parameters on days -1, 30, 60, 90, 120, 150, and 180 after the procedure. Among the metabolic parameters, we evaluated insulin secretion capacity-ISC (C peptide, RIA), metabolic control (HbA1c, chromatography), and insulin daily dose IDD. We found that C peptide levels increased, peaking on day 90 (A: 0.38 +/- 0.15; B: 0.34 +/- 0.19 nmol/L, P = NS) and then rapidly decreasing without differences, the HbA1c levels and IDD decreased in the same manner without differences between the groups. Our results demonstrate that multiple and single islet transplant regimens are equally efficient to temporarily restore a significant ISC with improvement of metabolic and clinical parameters. The results imply that the two regimens have an equal clinical value.

  16. Histidine-tryptophan-ketoglutarate for pancreas allograft preservation: the Indiana University experience.

    Science.gov (United States)

    Fridell, J A; Mangus, R S; Powelson, J A

    2010-05-01

    Histidine-tryptophan-ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation. A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1-year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (

  17. Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene.

    Science.gov (United States)

    Uin, Gan Shu; Maria, Notaridou; Ying, Fu Zhen; Kok Onn, Lee; Chuan, Sia Kian; Chunilal, Nathwani Amit; Marco, Della Peruta; Yorke, Calne Roy

    2016-01-01

    We report the correction of hyperglycemia of STZ induced diabetic mice using one intravenous systemic administration of a single stranded serotype 8 pseudotyped adeno-associated virus (ssAAV2/8) vector encoding the human proinsulin gene under a constitutive liver specific promoter. In vivo dose titration experiments were carried out and we identified an optimal range that achieved maintenance of euglycaemia or a mild diabetic condition for at least 9 months and ongoing to beyond 1 year for some animals, accompanied by human C-peptide secretion and weight gain. Further DNA codon optimization of the insulin gene construct resulted in approximately 3-10 times more human C-peptide secreted in the blood of codon optimized treated animals thereby reducing the number of vector particles required to achieve the same extent of reduction in blood glucose levels as the non-codon optimized vector. The constitutive secretion of insulin achieved with a single administration of the vector could be of therapeutic value for some diabetic patients. PMID:26795016

  18. Effects of leptin replacement therapy on pancreatic β-cell function in patients with lipodystrophy.

    Science.gov (United States)

    Muniyappa, Ranganath; Brown, Rebecca J; Mari, Andrea; Joseph, Jalaja; Warren, Mary A; Cochran, Elaine K; Skarulis, Monica C; Gorden, Phillip

    2014-04-01

    OBJECTIVE Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy. RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT. RESULTS There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance. CONCLUSIONS In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.

  19. Measurement of human proinsulin by an indirect two-site immunoradiometric assay

    International Nuclear Information System (INIS)

    An indirect two-site immunoradiometric assay is described for the measurement of human proinsulin in plasma. Polyethylene tubes coated with purified guinea-pig antibodies to insulin were used to extract proinsulin and insulin from plasma. Rabbit antibody to human C peptide was then added to react with C-peptide moiety of the bound proinsulin. The uptake of this antibody was measured by the subsequent binding of 125I-sheep antibody to rabbit IgG. The binding of radioactivity to the tubes was a function of the proinsulin concentration in the sample. The sensitivity of the assay was 0.006 pmol/ml. Only 200 μl of plasma was required in the assay and the 125I-labelled antibody was produced from readily available reagents. The polyethylene tubes remained stable for at least 5 months after coating. The mean fasting proinsulin level was 0.009 pmol/ml in sixteen normal subjects and 0.025 pmol/ml in twelve maturity onset diabetics. Oral glucose produced an 8 fold increase in proinsulin concentration but a decline in the plasma proinsulin/insulin molar ratio. Four patients with insulinoma had extremely elevated proinsulin levels and proinsulin/insulin ratios. (orig.)

  20. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity

    International Nuclear Information System (INIS)

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of β cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author)

  1. Proinsulin, GLP-1, and glucagon are associated with partial remission in children and adolescents with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Kaas, A.; Andersen, M. L. M.; Fredheim, Siri;

    2012-01-01

    Objective: Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA...... test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA). Results: Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p <0.0001, p = 0.0002). An...... inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p <0.0001) and IA (p = 0.0024, p = 0.0068, p <0.0001) at 1, 6, and 12 months. Glucagon (p <0.0001 and p <0.02) as well as GLP-1 (p = 0.0001 and p = 0...

  2. Myo-Inositol in the Treatment of Teenagers Affected by PCOS

    Science.gov (United States)

    Barbakadze, Ludmila; Kvashilava, Nana

    2016-01-01

    Objective. To compare the effectiveness of myo-inositol (MI) and oral contraceptive pills (OCPs) in monotherapy and MI in combination with OCPs in the treatment of teenagers affected by polycystic ovary syndrome (PCOS). Methods. 61 adolescent girls aged 13–19 years, with PCOS, were involved in the prospective, open-label study. Patients were randomized into three groups: I group, 20 patients receiving drospirenone 3 mg/ethinyl estradiol 30 μg; II group, 20 patients receiving 4 g myo-inositol plus 400 mg folic acid; III group, 21 patients receiving both medications. Results. After receiving MI significant reduction in weight, BMI, glucose, C-peptide, insulin, HOMA-IR, FT, and LH was detected. The levels of SHBG, TT, FAI, DHEA-S, and AMH did not change statistically significantly. After receiving OCPs weight and BMI slightly increased, but metabolic parameters did not change. Combination of MI and OCPs did not change weight and BMI, but reduction in C-peptide, insulin, and HOMA-IR was detected. TT, FT, FAI, DHEA-S, LH, and AMH levels decreased and SHBG increased. Conclusions. Administration of MI is a safe and effective method to prevent and correct metabolic disorders in teenagers affected by PCOS. With combination of MI and OCPs antiandrogenic effects are enhanced, negative impact of OCPs on weight gain is balanced, and metabolic profile is improved. PMID:27635134

  3. No Evidence of Viral Transmission following Long-Term Implantation of Agarose Encapsulated Porcine Islets in Diabetic Dogs

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    Lawrence S. Gazda

    2014-01-01

    Full Text Available We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n=3 was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652 when compared to a first macrobead implantation (days 9, 21, and 21 in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.

  4. Socioeconomic inequalities in lipid and glucose metabolism in early childhood in a population-based cohort: the ABCD-Study

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    van den Berg Gerrit

    2012-08-01

    Full Text Available Abstract Background Socioeconomic inequalities in cardiovascular disease are pervasive, yet much remains to be understood about how they originate. The objective of this study was to explore the relations of socioeconomic status to lipid and glucose metabolism as indicators of cardiovascular health in 5–6 year olds. Additionally to explore the explanatory role of maternal factors, birth outcome, and child factors. Methods In 1308 5–6 year old ethnic Dutch children from the ABCD cohort study, lipids (cholesterol, LDL, HDL, triglycerides, glucose and C-peptide were measured after an overnight-fast. Results There were no differences in cholesterol, HDL, LDL, and triglycerides between socioeconomic groups, as indicated by maternal education and income adequacy. However, children of low educated mothers had on average a higher glucose (β = 0.15; 95% confidence interval (CI 0.03 – 0.27, logC-peptide (β = 0.07; 95% CI 0.04 – 0.09, and calculated insulin resistance (HOMA-IR (β = 0.15; 95% CI 0.08 – 0.22 compared to children of high educated mothers. Only childhood BMI partly explained these differences (models controlled for age, height, and sex. Conclusions The socioeconomic gradient in cardiovascular risk factors seems to emerge in early childhood. In absence of underlying mechanisms these empirical findings are relevant for public health care and further explanatory research.

  5. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity; Desenvolvimento e padronizacao da tecnica de radioimunoensaio para a determinacao de pro-insulina humana e sua aplicacao no estudo do diabetes mellitus tipo II associado a obesidade

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Martha do

    1996-12-31

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of {beta} cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author) 133 refs., 17 figs., 36 tabs.

  6. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress) in Rats

    Science.gov (United States)

    Abdul Aziz, Siti Hajar; Nordin, Massita; Ramasamy, Rajesh; Adam, Aishah

    2016-01-01

    This study attempts to develop an experimental gestational diabetes mellitus (GDM) animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0). Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin), lipid profiles (total cholesterol, triglycerides, HDL, and LDL), genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1), glucose transporters (GLUT-2 and GLUT-4), proinflammatory cytokines (IL-6, TNF-α), and antioxidants (SOD, CAT, and GPX) on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations. PMID:27379252

  7. The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

    Science.gov (United States)

    Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

    2007-02-01

    Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

  8. Sitagliptin/Metformin Versus Insulin Glargine Combined With Metformin in Obese Subjects With Newly Diagnosed Type 2 Diabetes.

    Science.gov (United States)

    Ji, Ming; Xia, Libin; Cao, Jingzhu; Zou, Dajin

    2016-03-01

    To compare the therapeutic effects of different regimens in Chinese obese type 2 diabetic mellitus (T2DM) patients. From October 2013 to July 2014, a total of 166 T2DM outpatients who attended the Shanghai Changhai Hospital and the Yijishan Hospital of Wannan Medical College were randomly assigned into an experimental sitagliptin/metformin combined with low caloric diet group (n = 115) and an insulin glargine combined with metformin control group (n = 51). Inclusion criteria were body mass index (BMI) ≥ 25 kg/m and diagnosed with T2DM with glycosylated hemoglobin (glycated hemoglobin A1C [HbA1c]) >9%. Main outcome parameters were fasting plasma glucose, postprandial plasma glucose, BMI, HbA1c, fasting C-peptide, 2-h postprandial C-peptide, triglyceride (TG), total cholesterol (TC), high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C), which were determined by the 75 g steamed-bun meal tolerance test before and 4, 8, 12, and 24 weeks after the treatment started. Treatment costs and life quality were also assessed. BMI, HbA1C, TG, TC, and LDL were significantly more reduced (P 9%, oral sitagliptin/metformin combined with a low caloric diet effectively and economically maintained glycemic control and significantly improved life quality.

  9. Animal Model of Gestational Diabetes Mellitus with Pathophysiological Resemblance to the Human Condition Induced by Multiple Factors (Nutritional, Pharmacological, and Stress in Rats

    Directory of Open Access Journals (Sweden)

    Siti Hajar Abdul Aziz

    2016-01-01

    Full Text Available This study attempts to develop an experimental gestational diabetes mellitus (GDM animal model in female Sprague-Dawley rats. Rats were fed with high fat sucrose diet, impregnated, and induced with Streptozotocin and Nicotinamide on gestational day 0 (D0. Sleeping patterns of the rats were also manipulated to induce stress, a lifestyle factor that contributes to GDM. Rats were tested for glycemic parameters (glucose, C-peptide, and insulin, lipid profiles (total cholesterol, triglycerides, HDL, and LDL, genes affecting insulin signaling (IRS-2, AKT-1, and PCK-1, glucose transporters (GLUT-2 and GLUT-4, proinflammatory cytokines (IL-6, TNF-α, and antioxidants (SOD, CAT, and GPX on D6 and D21. GDM rats showed possible insulin resistance as evidenced by high expression of proinflammatory cytokines, PCK-1 and CRP. Furthermore, low levels of IRS-2 and AKT-1 genes and downregulation of GLUT-4 from the initial to final phases indicate possible defect of insulin signaling. GDM rats also showed an impairment of antioxidant status and a hyperlipidemic state. Additionally, GDM rats exhibited significantly higher body weight and blood glucose and lower plasma insulin level and C-peptide than control. Based on the findings outlined, the current GDM animal model closely replicates the disease state in human and can serve as a reference for future investigations.

  10. Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States.

    Science.gov (United States)

    Brennan, D C; Kopetskie, H A; Sayre, P H; Alejandro, R; Cagliero, E; Shapiro, A M J; Goldstein, J S; DesMarais, M R; Booher, S; Bianchine, P J

    2016-02-01

    We report the long-term follow-up of the efficacy and safety of islet transplantation in seven type 1 diabetic subjects from the United States enrolled in the multicenter international Edmonton Protocol who had persistent islet function after completion of the Edmonton Protocol. Subjects were followed up to 12 years with serial testing for sustained islet allograft function as measured by C-peptide. All seven subjects demonstrated continued islet function longer than a decade from the time of first islet transplantation. One subject remained insulin independent without the need for diabetic medications or supplemental transplants. One subject who was insulin-independent for over 8 years experienced graft failure 10.9 years after the first islet transplant. The remaining six subjects demonstrated continued islet function upon trial completion, although three had received a supplemental islet transplant each. At trial completion, five subjects were receiving insulin and two remained insulin independent, although one was treated with liraglutide. The median hemoglobin A1c was 6.3% (45 mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose ratio. No patients experienced severe hypoglycemia, opportunistic infection, or lymphoma. Thus, although the rate and duration of insulin independence was low, the Edmonton Protocol was safe in the long term. Alternative approaches to islet transplantation are under investigation. PMID:26433206

  11. 胰岛素瘤及正常胰腺组织中胰岛素原、胰岛素的表达%Expression of proinsulin and insulin in insulinoma and normal pancreas

    Institute of Scientific and Technical Information of China (English)

    杨海花; 李冲; 赵永福; 郑丽丽

    2011-01-01

    目的 检测胰岛素瘤及瘤旁正常胰腺组织中胰岛素、胰岛素原、C肽的表达水平,探讨它们的作用.方法 选取2006年9月至2009年12月确诊的38例胰岛素瘤及20例相应瘤旁正常胰腺组织标本,采用免疫组化染色的方法检测组织中胰岛素原、胰岛素、C肽的表达.结果 胰岛细胞瘤和瘤旁正常胰腺组织均表达胰岛素、C肽、胰岛素原.100%的胰岛素瘤组织胰岛素原和C肽强表达,而55%~60%正常胰腺组织为弱表达;79%的胰岛素瘤组织胰岛素表达为+++,而85%的正常胰腺组织胰岛素的表达为++++.38例胰岛素瘤的胰岛素原、C肽阳性表达细胞数占80%~100%,胰岛素阳性表达细胞数占50%~70%,胰岛素原/胰岛素>1占78.9%,正常胰腺组织分别为20%~80%、60%~90%、10.0%,两者差异均非常显著(P值均<0.05).结论 胰岛素瘤组织的胰岛素原/胰岛素>1者占78.9%,测定血浆胰岛素原可能有助于其诊断.%Objective To investigate the expression of proinsulin, insulin, C-peptide in insulinoma and normal pancreas and their roles. Methods Thirty-eight cases of insulinoma and 20 cases of normal pancreas from Sep. 2006 to Dec. 2009 in our hospital were selected. Immunohistochemistry was used to determine the expression of proinsulin, insulin, C-peptide. Results Proinsulin, insulin, C-peptide was expressed in insulinoma and normal pancreas. Proinsulin, C-peptide were strongly expressed in 100%insulinoma, while they were weekly expressed in 55% ~60% normal pancreas; insulin was expressed as + + +in 79% insulinoma, while it was expressed as + + + + in 85% normal pancreas. Proinsulin, C-peptide positive cell accounted for 80% ~ 100% of 38 insulinoma, and insulin positive cell accounted for 50% ~ 70%,the proinsulin/insulin ratio > 1 accounted for 78.9%; while the corresponding values were 20% ~ 80%, 60% ~90%, 10.0% in normal pancreas, and the difference was statistically significant ( P < 0

  12. A multicenter clinical study to determine the efficacy of a novel fenugreek seed (Trigonella foenum-graecum) extract (Fenfuro™) in patients with type 2 diabetes

    Science.gov (United States)

    Verma, Narsingh; Usman, Kauser; Patel, Naresh; Jain, Arvind; Dhakre, Sudhir; Swaroop, Anand; Bagchi, Manashi; Kumar, Pawan; Preuss, Harry G.; Bagchi, Debasis

    2016-01-01

    Background Trigonella foenum-graecum (fenugreek) seeds are known to exhibit potent antioxidant, hypoglycemic, and nephroprotective activities, as well as serve as excellent membrane stabilizers especially because of their content of novel furostanolic saponins. Our previous studies exhibited the broad spectrum safety and efficacy of Fenfuro, a novel T. foenum-graecum seed extract enriched in furostanolic saponins, in type 2 diabetes (T2D) in rats. Design This multicenter, randomized, placebo-controlled, double-blind, add-on clinical study evaluated over a period of 90 consecutive days the efficacy of Fenfuro (daily dosage: 500 mg bid) in 154 subjects (male: 108; female: 46; age: 25–60 years) with T2D. Methods This study examined the body weight, blood pressure, and pulse rate, as well as the efficacy of Fenfuro on fasting and post-prandial plasma sugar (mg/dL), glycosylated hemoglobin (HbA1c), and fasting and post-prandial C-peptide levels. Results Fenfuro caused significant reduction in both fasting plasma and post-prandial blood sugar levels. Approximately 83% of the subjects reported decreases in fasting plasma sugar levels in the Fenfuro-treated group as compared to 62% in the placebo group, while 89% of the subjects demonstrated reduction in post-prandial plasma sugar levels in the Fenfuro-treated group as compared to 72% in the placebo group. HbA1c levels were reduced in both placebo and treatment groups. The decrease in HbA1c levels was significant in both groups as compared to respective baseline values. A significant increase in fasting and post-prandial C-peptide levels compared to the respective baseline values was observed, while no significant changes in fasting and post-prandial C-peptide levels were observed between the two groups. No significant adverse effects were observed by blood chemistry analyses. Furthermore, 48.8% of the subjects reported reduced dosage of anti-diabetic therapy in the Fenfuro-treated group, whereas 18.05% reported reduced

  13. MECHANISMS OF ACTION OF THE POWDER OF CURCUMA LONGA RHIZOME PLANT ON A CARBOHYDRATE METABOLISM AT ALLOXAN-INDUCED DIABETIC RATS

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    R. I. Aizman

    2014-01-01

    Full Text Available Aim. The effects of the powder of Curcuma longa plant rhizome as food additive on different processes of carbohydrate metabolism: glucose concentration in whole blood, concentration of hormones – insulin and C-peptide in plasma, content of glycogen in the liver, structural and functional organization of the islet apparatus of the pancreas in rats with alloxan-induced diabetes mellitus were studied.Material and methods. The study was conducted on Wistar adult male rats. All animals were divided into 4 groups: 1 and 2 – the controls, 3 and 4 – the rats with alloxan-induced model of diabetes mellitus. Animals of groups 1 and 3 were kept on standard chow, whereas the rats of groups 2 and 4 were feeded with additive of powder from Curcuma longa plant rhizome (2% by weight of feed.The concentration of glucose in blood and perfused solution was determined with picric acid method by intensity of colour reaction on spectrofotometer. Concentration of hormones (insulin, C-peptide was defined by immunoenzyme method with standard sets on tablet spectrofotometer. The morphological structure of a pancreas was studied by a method of light microscopy. Content of glycogen in a liver was measured by means of Shick-reaction on the Mac-Manus method with measurement of colour intensity on spectrofotometer.Results. Intake of the turmeric rhizomes powder by rats with diabetes, as compared with the diabetic animals on a standard diet, resulted in the lower increase of the glucose concentration in blood, the decrease of glucose absorption in the gut, higher concentration of the insulin and C-peptide in plasma and significant increase of glycogen content in the liver. The microstructure of pancreatic tissue samples of experimental animals using turmeric intake, was characterized by the better preservation of the islet apparatus in comparison with a group of animals on a standard diet.Conclusion. The results indicate the positive effect of the Curcuma longa

  14. Hypo glycemic and Hypolipidaemic Effect of cinnamon Extract in Diabetic and irradiated Rats

    International Nuclear Information System (INIS)

    This study was made to investigate the antidiabetic and hypolipidemic potential of cinnamon against radiation and/or streptozotocin (STZ) induced diabetes in rats. In the experiment, a total of 36 rats were used and the rats were divided into six groups each of six rats: group 1, normal untreated rats; group 2, animals received only cinnamon (200 mg/kg/day) for 30 consecutive days; group 3, animals exposed to 4 Gy whole body gamma radiation as a single shot dose; group 4, animals were injected intraperitoneally with a freshly prepared solution of streptozotocin (45 mg/kg) in 0.1 M citrate buffer, ph 4.5; group 5, rats were injected intraperitoneally with a freshly prepared solution of streptozotocin (45 mg/kg), followed by irradiation at a dose level of 4 Gy; and group 6, rats were given orally cinnamon (200 mg/kg/day) for 30 days then injected intraperitoneally with a freshly prepared solution of streptozotocin followed by irradiation at a dose level of 4 Gy. Blood samples were collected from all groups for the determination of serum fasting blood sugar (FBG), glycidate hemoglobin (HbA1c), plasma insulin, serum C-peptide, serum total cholesterol (TC), Serum triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). In diabetic and irradiated groups there was a highly significant increase in the percentage of (HbA1c) and concentration of FBG, TC, TG, LDL-C and a significant decrease in the level of HDL-C, plasma insulin and C-peptide compared to those of control group. Treatment of the diabetic irradiated rats with cinnamon caused a significant decrease in the percentage of HbA1c and concentration of FBG, TC, TG, LDL-C and significant increase in the level of HDL-C, plasma insulin and C-peptide compared to the diabetic irradiated rats. On the basis of these results, one could conclude that cinnamon exhibit hypo glycemic and hypolipidaemic properties and could be considered a promising agent for diabetes

  15. Beneficial effects of a diabetes specific formula on insulin sensitivity and free fatty acid in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    LI Yu-xiu; ZENG Jing-bo; YU Kang; SUN Qi; LIU Qiu-ying; QIN Wei; ZHANG Qian; YU Jian-chun; WANG Heng

    2008-01-01

    Background This prospective, randomized, controlled study was designed to investigate the effects of a diabetes specific formula (Diason low energy:313.8 kJ/100 ml),compared with a standard formula, on insulin sensitivity, serum C peptide, serum lipids and free fatty acid(FFA)in type 2 diabetics. Methods In total of 71 type 2 diabetics completed the study. Enteral formulas were given orally as the sole source of nutrition to the subjects for 6 days. Venous blood samples(0.5,1,2,3 hours)were collected at day-7 after a 75 g oral glucose tolerance test(OGTT),day 1 after a standard test meal(1673.6 kJ)and after 6 days of either the test diabetes specific formula or a standard formula. Plasma glucose,serum insulin, C peptide and lipids were. measured. Results After the intervention period, the diabetes specific formula resulted in a significantly lower postprandial rise in blood glucose concentrations at 0.5 hour(P<0.05)and 1 hour(P<0.01);significantly lower peak height of plasma glucose(P=0.05);significantly lower plasma insulin concentrations at 0.5 hour(P<0.01),1 hour(P<0.01)and 2 hours(P<0.01);and a significantly lower plasma insulin peak compared to controls; both OGTT and a standard test meal(P<0.05).The glucose and insulin area under the curve after the diabetes specific formula compared to the standard formula were significantly lower. The C peptide level was lower after 6 days of both nutrition formulas compare to 75 g OGTT, but not different from the standard mixed meal. Both formulas were well toleraled. Conclusions In summary the diabetes specific formula with a relatively high monounsaturated fatty acid and high multi fiber proportion significantly improved glycemic control. On top of this,the insulin sensitivity(HOMA-IS)was significantly improved and may therefore directly improve the impact on long term complications. The disease specific formula should therefore be the preferred option to be used by diabetic and hyperglycemic patients in need

  16. Autologous bone marrow stem cell transplantation for the treatment of type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    WANG Li; ZHAO Shi; MAO Hong; ZHOU Ling; WANG Zhong-jing; WANG Hong-xiang

    2011-01-01

    Background Autologous peripheral stem cell transplantation was first reported in 2007 to treat type 1 diabetes mellitus (DM) and achieved encouraging effect,but whether similar outcome can be achieved in type 2 DM is not well demonstrated.The objective of this study was to determine the effect of combination of autologous bone marrow stem cell transplantation (BMT) and hyperbaric oxygen treatment on type 2 DM.Methods The study involved 31 patients with type 2 DM (aged 33 to 62 years) from January 2009 to January 2011 in the Central Hospital of Wuhan,China.Clinical variables (body mass index,duration of DM,insulin requirement,oral hypoglycemic drugs,time free from insulin,time free from oral drugs) and laboratory variables (hemoglobin A1c (HbA1c)),mononuclear cells infused,and C-peptide in four time points) were assessed.Purified bone marrow stem cells were infused into major pancreatic arteries.Follow-up was performed at the 30,90,180,360,540 and 720 days (mean 321 days) after BMT.Results Mean HbA1c values showed a significant reduction during follow-up in all patients after BMT.It decreased by more than 1.5% (from 8.7% to 7.1%) as quickly as at 30 days after BMT.Afterwards mean HbA1c fluctuated between plus or minus 0.5% until 24 months rather than declined continuously.At 90 days after the combined therapy C-peptide increased significantly compared with baseline (P <0.0001).But in other time points C-peptide was similar with baseline data (P>0.3).All patients had insulin and/or oral hypoglycemic drugs reduced to different levels.The dose of insulin of 7 patients (7/26,27%) reduced for a period of time after BMT.Conclusions Combined therapy of intrapancreatic BMT and hyperbaric oxygen treatment can improve glucose control and reduce the dose of insulin and/or oral hypoglycemic drugs in type 2 DM patients,but it only improve pancreatic β-cell function transiently.Further randomized controlled clinical trials involved more patients will be required to

  17. 高血压合并糖尿病妊娠临床分析%Clinical analysis of hypertension of preynancy associated with diabetes

    Institute of Scientific and Technical Information of China (English)

    赵昕

    2015-01-01

    Objective To observe the clinical features of pregnancy associated with diabetes hypertension. Methods Choose 2009 danuary to 2013 danuary 100 cases of hypertension of pregnancy associated with diabetes in pregnant women as the study group, 100 healthy pregnant women as control group, the two groups of pregnant women, insulin, C peptide, HbAlc, CRP, IL-6, TNF-al-pha several indicators than care to. Results The levels of blood glucose, several indexes of blood lipids, insulin, C peptide, HbAlc, CRP, IL-6, TNF- alpha study group 100 cases of pregnant women were significantly higher than those in the control group 100 cases of pregnant women, P<0.05. Conclusion The increase of hypertension and diabetes in pregnancy and pregnant women in vi-vo insulin, C peptide, HbAlc, CRP, IL-6, TNF-alpha level has a specific relationship, should be paid attention to.%目的:观察高血压合并糖尿病妊娠的临床特点。方法2009年1月—2013年1月收治的100例高血压合并糖尿病妊娠的孕妇为研究组,100名健康孕妇为对照组,对两组孕妇的胰岛素、C肽、HbAlc、CRP、IL-6、TNF-α几项指标加以比较。结果研究组100例孕妇的血糖、血脂、胰岛素、C肽、HbAlc、CRP、IL-6、TNF-α几项指标水平均显著高于对照组100名孕妇,P<0.05。结论高血压合并糖尿病妊娠与孕妇体内胰岛素、C肽、HbAlc、CRP、IL-6、TNF-α水平升高具有特异性关系,应当得到重视。

  18. Pancreatic insulin-producing cells differentiated from human embryonic stem cells correct hyperglycemia in SCID/NOD mice, an animal model of diabetes.

    Directory of Open Access Journals (Sweden)

    Xiu-feng Hua

    Full Text Available Human pancreatic islet transplantation is a prospective curative treatment for diabetes. However, the lack of donor pancreases greatly limits this approach. One approach to overcome the limited supply of donor pancreases is to generate functional islets from human embryonic stem cells (hESCs, a cell line with unlimited proliferative capacity, through rapid directed differentiation. This study investigated whether pancreatic insulin-producing cells (IPCs differentiated from hESCs could correct hyperglycemia in severe combined immunodeficient (SCID/non-obese diabetic (NOD mice, an animal model of diabetes.We generated pancreatic IPCs from two hESC lines, YT1 and YT2, using an optimized four-stage differentiation protocol in a chemically defined culture system. Then, about 5-7 × 10(6 differentiated cells were transplanted into the epididymal fat pad of SCID/NOD mice (n = 20. The control group were transplanted with undifferentiated hESCs (n = 6. Graft survival and function were assessed using immunohistochemistry, and measuring serum human C-peptide and blood glucose levels.The pancreatic IPCs were generated by the four-stage differentiation protocol using hESCs. About 17.1% of differentiated cells expressed insulin, as determined by flow cytometry. These cells secreted insulin/C-peptide following glucose stimulation, similarly to adult human islets. Most of these IPCs co-expressed mature β cell-specific markers, including human C-peptide, GLUT2, PDX1, insulin, and glucagon. After implantation into the epididymal fat pad of SCID/NOD mice, the hESC-derived pancreatic IPCs corrected hyperglycemia for ≥ 8 weeks. None of the animals transplanted with pancreatic IPCs developed tumors during the time. The mean survival of recipients was increased by implanted IPCs as compared to implanted undifferentiated hESCs (P<0.0001.The results of this study confirmed that human terminally differentiated pancreatic IPCs derived from hESCs can correct

  19. Regular consumption of pulses for 8 weeks reduces metabolic syndrome risk factors in overweight and obese adults.

    Science.gov (United States)

    Mollard, R C; Luhovyy, B L; Panahi, S; Nunez, M; Hanley, A; Anderson, G H

    2012-08-01

    Pulses are low in energy density, supporting their inclusion in the diet for the management of risk factors of the metabolic syndrome (MetSyn). The aim of the present study was to describe the effects of frequent consumption (five cups/week over 8 weeks) of pulses (yellow peas, chickpeas, navy beans and lentils), compared with counselling to reduce energy intake by 2093 kJ/d (500 kcal/d), on risk factors of the MetSyn in two groups (nineteen and twenty-one subjects, respectively) of overweight or obese (mean BMI 32·8 kg/m2) adults. Body weight, waist circumference, blood pressure, fasting blood parameters and 24 h food intakes were measured at weeks 1, 4 and 8. Blood glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and ghrelin were measured after a 75 g oral glucose load at weeks 1 and 8. At week 8, both groups reported reductions in energy intake, waist circumference, systolic blood pressure, glycosylated Hb (HbA1c) and glucose AUC and homeostasis model of insulin resistance (HOMA-IR) following the glucose load (P < 0·05). However, HDL, fasting C-peptide and insulin AUC responses were dependent on diet (P < 0·05). HDL and C-peptide increased by 4·5 and 12·3 %, respectively, in the pulse group, but decreased by 0·8 and 7·6 %, respectively, in the energy-restricted group. Insulin AUC decreased in both females and males on the energy-restricted diet by 24·2 and 4·8 %, respectively, but on the pulse diet it decreased by 13·9 % in females and increased by 27·3 % in males (P < 0·05). In conclusion, frequent consumption of pulses in an ad libitum diet reduced risk factors of the MetSyn and these effects were equivalent, and in some instances stronger, than counselling for dietary energy reduction. PMID:22916807

  20. Sample size requirements for studies of treatment effects on beta-cell function in newly diagnosed type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    John M Lachin

    Full Text Available Preservation of β-cell function as measured by stimulated C-peptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet, repeated 2-hour Mixed Meal Tolerance Tests (MMTT were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2-hour area under the curve (AUC of the C-peptide values. The natural log(x, log(x+1 and square-root (√x transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of follow-up and among children 8-12 years of age, adolescents (13-17 years and adults (18+ years. The sample size needed to detect a given relative (percentage difference with treatment versus control is greater at 24 months than at 12 months of follow-up, and differs among age categories. Owing to greater residual variation among those 13-17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(x+1 and √x transformed values in terms of the original units of measurement (pmol/ml. Analyses using different transformations are described for the TrialNet study of masked anti-CD20 (rituximab versus masked placebo. These results provide the information needed to

  1. Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

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    A. V. Vanikar

    2010-01-01

    Full Text Available Aims. Insulin dependent diabetes mellitus (IDDM is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT, 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC and cultured bone marrow (CBM as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4 patients with 1–24-year disease duration, in age group: 13–43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac: 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1×103/μL, CD45−/90+/73+:40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1×103/μL, CD45−/34+:0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques.

  2. Effects of a Follow-On Formula Containing Isomaltulose (Palatinose™ on Metabolic Response, Acceptance, Tolerance and Safety in Infants: A Randomized-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    M Fleddermann

    Full Text Available Effects of the dietary glycaemic load on postprandial blood glucose and insulin response might be of importance for fat deposition and risk of obesity. We aimed to investigate the metabolic effects, acceptance and tolerance of a follow-on formula containing the low glycaemic and low insulinaemic carbohydrate isomaltulose replacing high glycaemic maltodextrin. Healthy term infants aged 4 to 8 completed months (n = 50 were randomized to receive the intervention follow-on formula (IF, 2.1g isomaltulose (Palatinose™/100mL or an isocaloric conventional formula (CF providing 2.1g maltodextrin/100mL for four weeks. Plasma insulinaemia 60 min after start of feeding (primary outcome was not statistically different, while glycaemia adjusted for age and time for drinking/volume of meal 60 min after start of feeding was 122(105,140 mg/dL in IF (median, interquartile range and 111(100,123 in CF (p = 0.01. Urinary c-peptide:creatinine ratio did not differ (IF:81.5(44.7, 96.0 vs. CF:56.8(37.5, 129,p = 0.43. Urinary c-peptide:creatinine ratio was correlated total intake of energy (R = 0.31,p = 0.045, protein (R = 0.42,p = 0.006 and fat (R = 0.40,p = 0.01 but not with carbohydrate intake (R = 0.22,p = 0.16. Both formulae were well accepted without differences in time of crying, flatulence, stool characteristics and the occurrence of adverse events. The expected lower postprandial plasma insulin and blood glucose level due to replacement of high glycaemic maltodextrin by low glycaemic isomaltulose were not observed in the single time-point blood analysis. In infants aged 4 to 8 completed months fed a liquid formula, peak blood glucose might be reached earlier than 60 min after start of feeding. Non-invasive urinary c-peptide measurements may be a suitable marker of nutritional intake during the previous four days in infants.ClinicalTrials.gov NCT01627015.

  3. Association between insulin resistance and breast carcinoma: a systematic review and meta-analysis.

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    Adrian V Hernandez

    Full Text Available OBJECTIVE: This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. STUDY DESIGN: We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. RESULTS: Twenty-two studies (n = 33,405 were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD -0.03, 95%CI -0.32 to 0.27; p = 0.9. Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, -0.21 to 0.34; p = 0.6. Using individual odds ratios (ORs adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1 of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38. Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92. Homeostatic model assessment (HOMA-IR levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001. CONCLUSIONS: Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.

  4. Autologous hematopoietic stem cell transplantation and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes: long term follow-up

    Institute of Scientific and Technical Information of China (English)

    Gu Yi; Gong Chunxiu; Peng Xiaoxia; Wei Liya; Su Chang; Qin Miao; Wang Xi'ou

    2014-01-01

    Background It has been indicated that autologous hematopoietic stem cell transplantation (AHST) is a promising treatment to adults with type 1 diabetes,however,the application of AHST therapy to children with type 1 diabetes still needs more data.The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes.Methods This 1:2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology,Beijing Children's Hospital from 2009-2010.The case group included 14 patients,who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010.The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization.We compared the baseline and follow-up data of them,including ketoacidosis onset,clinical variables (glycosylated hemoglobin (HbA1c),insulin dosage and serum C-peptide).Results The clinical characteristics of the patients was comparable between the case group and the control group.At 6-12 months ((10.7±4.2) months) after AHST treatment,we found 11 patients in the case group did not stop the insulin therapy,three cases stopped insulin treatment for 2,3 and 11 months,respectively.No diabetic ketoacidosis (DKA) occurred after transplantation in all the patients in the case group.HbA1c in the control group was significant lower than that in the case group (P <0.01),while the insulin dosage and serum C-peptide were not significant different between the two groups (P >0.05).In order to eliminate the honeymoon effect,we performed final follow-up at the 3-5 years ((4.2±1.8) years) after AHST treatment,and found that HbA1c in the control group was still lower than that in the case group (P <0.01); however,the insulin dosage and serum C-peptide were not

  5. Plasma Levels of the Interleukin-1-Receptor Antagonist Are Lower in Women with Gestational Diabetes Mellitus and Are Particularly Associated with Postpartum Development of Type 2 Diabetes.

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    Pernilla Katra

    Full Text Available Diabetes mellitus is a group of diseases characterized by chronic hyperglycemia. Women who develops hyperglycemia for the first time during pregnancy receive the diagnosis gestational diabetes mellitus (GDM. Presently, there is no consensus about the diagnostic criteria for GDM. A majority of these women subsequently develop postpartum overt diabetes making it important to identify these patients as early as possible. In this study we investigated if plasma levels of the interleukin-1 receptor antagonist (IL-1Ra, an endogenous inhibitor of IL-1 signaling, can be used as a complementary biomarker for diagnosing GDM and predicting postpartum development of overt diabetes mellitus. Patients participating in this study (n = 227 were diagnosed with their first GDM 2004-2013 at Lund University Hospital, Lund, Sweden. Healthy pregnant volunteers (n = 156 were recruited from women's welfare centers in the same region 2014-2015. Levels of IL-1Ra and C-peptide were analyzed in ethylenediaminetetraacetic acid (EDTA-plasma or serum using enzyme linked immunosorbent assay (ELISA. GDM patients had significantly lower levels of IL-1Ra than the control group (p = 0.012. In addition, GDM patients that had developed impaired glucose tolerance (IGT or type 2 diabetes mellitus postpartum had significantly lower levels of IL-1Ra, and significantly higher levels of C-peptide than GDM patients that had not developed diabetes mellitus postpartum (p = 0.023 and (p = 0.0011 respectively. An inverse correlation was found between IL-1Ra and serum C-peptide levels in the control group (rs = -0.31 p = 0.0001. Our results show that IL-1Ra might be included in a future panel of biomarkers, both for diagnosing GDM to complement blood glucose, and also identifying GDM patients that are at risk of developing type 2 diabetes mellitus postpartum. However, the ROC curve analysis provided a sensitivity of 52.2% and specificity of 67.1%, which nonetheless may not be sufficient enough

  6. Plasma Levels of the Interleukin-1-Receptor Antagonist Are Lower in Women with Gestational Diabetes Mellitus and Are Particularly Associated with Postpartum Development of Type 2 Diabetes.

    Science.gov (United States)

    Katra, Pernilla; Dereke, Jonatan; Nilsson, Charlotta; Hillman, Magnus

    2016-01-01

    Diabetes mellitus is a group of diseases characterized by chronic hyperglycemia. Women who develops hyperglycemia for the first time during pregnancy receive the diagnosis gestational diabetes mellitus (GDM). Presently, there is no consensus about the diagnostic criteria for GDM. A majority of these women subsequently develop postpartum overt diabetes making it important to identify these patients as early as possible. In this study we investigated if plasma levels of the interleukin-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1 signaling, can be used as a complementary biomarker for diagnosing GDM and predicting postpartum development of overt diabetes mellitus. Patients participating in this study (n = 227) were diagnosed with their first GDM 2004-2013 at Lund University Hospital, Lund, Sweden. Healthy pregnant volunteers (n = 156) were recruited from women's welfare centers in the same region 2014-2015. Levels of IL-1Ra and C-peptide were analyzed in ethylenediaminetetraacetic acid (EDTA)-plasma or serum using enzyme linked immunosorbent assay (ELISA). GDM patients had significantly lower levels of IL-1Ra than the control group (p = 0.012). In addition, GDM patients that had developed impaired glucose tolerance (IGT) or type 2 diabetes mellitus postpartum had significantly lower levels of IL-1Ra, and significantly higher levels of C-peptide than GDM patients that had not developed diabetes mellitus postpartum (p = 0.023) and (p = 0.0011) respectively. An inverse correlation was found between IL-1Ra and serum C-peptide levels in the control group (rs = -0.31 p = 0.0001). Our results show that IL-1Ra might be included in a future panel of biomarkers, both for diagnosing GDM to complement blood glucose, and also identifying GDM patients that are at risk of developing type 2 diabetes mellitus postpartum. However, the ROC curve analysis provided a sensitivity of 52.2% and specificity of 67.1%, which nonetheless may not be sufficient enough to use IL

  7. UV-laser-assisted modification of poly(methyl methacrylate) and its application to capillary-driven-flow immunoassay

    Science.gov (United States)

    Fuchiwaki, Y.; Takaoka, H.

    2015-07-01

    A concave microchannel surface was formed by nanosecond pulse laser ablation to allow antibody immobilization on a capillary flow immunoassay chip. Microscopic analysis showed that UV laser ablation of poly(methyl methacrylate) at 193 nm and 1.76 J · cm-2 allowed excellent immobilization of Cy5 conjugated antibody. The concave structure was 10 µm deep and 260 µm wide and supported uniform antibody printing on the microchannel surface. The characteristics of immobilized antibodies on this surface and on a commercially available polymer coating were comparable. Quantitative analysis of procollagen type I C-peptide (PICP) at different concentrations provided a linear relationship in the range 0-600 ng ml-1 PICP, which is sufficient for clinical estimation of PICP in the blood. The results may provide a new benchmark for a mechatronic antibody immobilization-based capillary flow immunoassay chip.

  8. B islet cells of pancreas are the site of expression of the human insulin gene in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Bucchini, D.; Desbois, P.; Pictet, R.; Jami, J. (Univ. Paris 7 (France)); Madsen, O. (Hagedorn Research Lab., Gentofte (Denmark))

    1989-02-01

    Transgenic mouse lines carrying the human insulin gene were previously shown to express it in pancreas but not in other tissues. The present study reports evidence that the expression of the transgene is restricted to a single category of cells. Immunofluorescence staining of frozen pancreas sections showed that the human C-peptide was present in pancreatic islets only, and more precisely in the B cells of the islets. Human insulin transcripts were initiated correctly in mouse pancreas at the same site as in human pancreas. Three different transgenic lines with different insertion sites and various copy numbers of the human insulin transgene had the same high levels of the transgene transcripts corresponding to a well-balanced contribution in insulin gene expression.

  9. A PROSPECTIVE STUDY OF EFFECT OF REPAGLINIDE MONOTHERAPY VERSUS ITS COMBINATION WITH METFORMIN IN TYPE 2 DIABETES MELLITUS PATIENTS

    Directory of Open Access Journals (Sweden)

    Ateeq Akbar

    2016-03-01

    Full Text Available BACKGROUND Diabetes mellitus is a chronic metabolic disorder and complications are due to persistent hyperglycaemia. So to prevent or delay the complication, near-euglycaemia needs to be achieved. For that various drugs are used. MATERIAL AND METHODS This is a prospective, randomised open labelled study conducted in the Department of General Medicine, Amalapuram. Various parameters were measured before and after 16 weeks of study like FPG, PPPG, HbA1c, LDL, TG, and total cholesterol. RESULTS There was decrease in all the parameters in both the groups, but c-peptide level was decreased more in group B than group A and also increase in HDL concentration was more in group B. CONCLUSION When one antidiabetic drug is not sufficient to maintain euglycaemia and to prevent complication, various combinations are used. So various drug combinations to be evaluated and study to be conducted to establish the efficacy and more therapeutic options.

  10. Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection

    DEFF Research Database (Denmark)

    Ekholm, E; Shaat, N; Holst, Jens Juul

    2012-01-01

    The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from.......8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P

  11. Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

    DEFF Research Database (Denmark)

    Vestergaard, H; Weinreb, J E; Rosen, A S;

    1995-01-01

    A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus, longitu......A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......-maintaining diet. Gliclazide treatment results in increased serum C-peptide, decreased hemoglobin-A1c, decreased glucose excursion on glucose tolerance test, and 35% increased insulin-stimulated glucose disposal. Gliclazide therapy is not associated with any change in DNA or protein content per g muscle or any...

  12. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Taskiran, M; Toft-Nielsen, M B;

    2001-01-01

    ) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect...... this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally......) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2...

  13. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Pedersen, Bente K;

    2014-01-01

    : 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m(2), P > 0.05) underwent a 180-min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6-(2)H2]glucose and ingestion of [U-(13)C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials......, plasma glucose concentrations and kinetics, insulin, C-peptide, and glucagon were measured. Rates (mg kg(-1) min(-1)) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; Ra OGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, Ra...

  14. The 12th quality control survey for radioisotope in vitro tests in Japan, 1990

    Energy Technology Data Exchange (ETDEWEB)

    1991-10-01

    The results of the 12th quality control nationwide survey is presented. Of 670 selected facilities, 405 (60.4%) participated in this survey. Myoglobin and trypsin were added as new items to be examined. The other conventional items were as follows: alpha-fetoprotein (AFP), aldosterone, {beta}{sub 2}-microglobulin, carbohydrate angigen 15-3, C-peptide, digoxin, elastase 1, free triiodothyronine, growth hormone, immunoglobulin E, prostatic acid phosphatase, pancreatic secretory trypsin inhibitor, progesterone, prolactin, thyroglobulin, triiodothyronine (T{sub 3}), T{sub 3} uptake, tissue polypeptide antigen, thyroid stimulating hormone, and testosterone. There was a great coefficient of variation (CV) between kits in AFP, aldosterone, progesterone, and prolactin. These results were analogous to those in the previous surveys. For T{sub 3}, there was a great difference between CV by radioimmunoassay and by non-isotopic method. Both myoglobin and trypsin had a great difference between kits. (N.K.).

  15. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1

    DEFF Research Database (Denmark)

    Jensen, Majken K; Koh-Banerjee, Pauline; Franz, Mary;

    2006-01-01

    BACKGROUND: Intake of whole grains is inversely associated with risk of diabetes and ischemic heart disease in observational studies. The lower risk associated with high whole-grain intakes may be mediated through improvements in glycemic control, lipid profiles, or reduced inflammation. OBJECTIVE......: The aim was to examine whether the intake of whole grains, bran, and germ is related to homocysteine, plasma markers of glycemic control (fasting insulin, hemoglobin A1c, C-peptide, and leptin), lipids (total cholesterol, triacylglycerol, HDL cholesterol, and LDL cholesterol), and inflammation (C....... Inverse associations were also observed with total cholesterol (P = 0.02), HDL cholesterol (P = 0.05), and LDL cholesterol (P = 0.10). Whole-grain intake was not associated with the markers of inflammation. Whole-grain intake was most strongly inversely associated with markers of glycemic control...

  16. Ethnic Differences in Insulin Sensitivity, β-Cell Function, and Hepatic Extraction Between Japanese and Caucasians

    DEFF Research Database (Denmark)

    Møller, Jonas B; Dalla Man, Chiara; Overgaard, Rune V;

    2014-01-01

    a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of β-cell function, hepatic extraction, and insulin...... sensitivity were assessed using C-peptide, glucose, and insulin minimal models. RESULTS: Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P < .01). In subjects with IGT, estimates of the dynamic (Φ(d)) and static (Φ(s)) β-cell responsiveness were significantly lower in the Japanese...... compared with Caucasians (P < .05). In contrast, values of insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P < .01). Despite differences in insulin sensitivity, β-cell function, and...

  17. Transplantation of mesenchymal stem cells improves type 1 diabetes mellitus.

    Science.gov (United States)

    Li, Lisha; Li, Furong; Gao, Feng; Yang, Yali; Liu, Yuanyuan; Guo, Pingping; Li, Yulin

    2016-05-01

    Bone-marrow-derived stem cells can regenerate pancreatic tissue in a model of type 1 diabetes mellitus. Mesenchymal stem cells (MSCs) form the main part of bone marrow. We show that the intrapancreatic transplantation of MSCs elevates serum insulin and C-peptide, while decreasing blood glucose. MSCs engrafted into the damaged rat pancreas become distributed into the blood vessels, acini, ducts, and islets. Renascent islets, islet-like clusters, and a small number of MSCs expressing insulin protein have been observed in the pancreas of diabetic rats. Intrapancreatic transplantation of MSCs triggers a series of molecular and cellular events, including differentiation towards the pancreas directly and the provision of a niche to start endogenous pancreatic regeneration, which ameliorates hypoinsulinemia and hyperglycemia caused by streptozotocin. These data establish the many roles of MSCs in the restoration of the function of an injured organ. PMID:26650464

  18. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure.

    Science.gov (United States)

    Sun, Bo; Roh, Kyung-Hwan; Lee, Sae-Rom; Lee, Yong-Soon; Kang, Kyung-Sun

    2007-03-23

    Success in islet-transplantation-based therapies for type I diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Embryonic stem cells (ESCs) have been successfully induced into insulin producing islet-like structure in several studies. However, the source of the ESCs has presented ethical and technical concerns. Here, we isolated a population of stem cells from human cord blood (UCB), which expressed embryo stage specific maker, SSEA-4, and the multi-potential stem cell marker, Oct4. Subsequently, we successfully induced them into insulin-producing islet-like structures, which co-express insulin and C-peptide. These findings might have a significant potential to advance human UCB derived stem-cell-based therapeutics for diabetes.

  19. Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Hua; Yanwei Wang; Peiwen Lian; Shouxin Zhang; Jianyuan Li; Haiyan Wang; Shulin Chen; Wei Gao

    2012-01-01

    Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14-20 weeks.They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein.These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network.Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expressing insulin and glucagon, with an islet-like morphology.These cells had glucose-stimulated secretion of human insulin and C-peptide.Results suggest that pancreatic stem cells can be differentiated into neuron-like and islet-like cells.

  20. Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely

    DEFF Research Database (Denmark)

    Cioffi, Iolanda; Santarpia, Lidia; Vaccaro, Andrea;

    2016-01-01

    In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different...... isocaloric lunch meals, consisting of (i) refined-grain pasta (RG+T), (ii) whole-grain pasta (WG+T), (iii) lemon juice-supplemented refined-grain pasta (LRG+T), and (iv) refined-grain pasta with legumes (RG+L), were administered to 8 healthy participants in a crossover design. On the test days, participants...... glucose (p = 0.001) was lower for RG+T, and triacylglycerols (p = 0.02) increased for LRG+T; however, insulin, C-peptide, and ghrelin were comparable in all other meals. In conclusion, our study indicates that acute consumption of whole-grain pasta may promote fullness and reduce hunger, lowering...

  1. Alterations of Cell-Mediated Immunity in Patients with Type 2 Diabetes Mellitus%2型糖尿病细胞免疫功能的变化

    Institute of Scientific and Technical Information of China (English)

    姚远; 郑佳; 杨敏

    2002-01-01

    Objective To investigate the alterations of cell- mediated immunity in patients with type 2 diabetes mellitus. Methods The level of CD3 CD4 CD8 in 30 normal subjects (NC group) and47 type 2 diabetes mellitus was measured by flow cytometry. Result Type - 2 diabetics had lower levels of CD4 and higher levels of CD8 than the non - diabetic control,especially during the 5 ~ 15 years of diabetes courses. The ratios of CD4 to CD8 was decreased. The correlation analysis showed that the level of CD3 CD4 CD8 and CD4/CD8 was not positively correlated with c - peptide. Conclusion Type - 2 diabeties have alterations of cell- mediated immunity.

  2. Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

    DEFF Research Database (Denmark)

    Gjesing, Anette P; Ribel-Madsen, Rasmus; Harder, Marie N;

    2015-01-01

    AIMS/HYPOTHESIS: We examined the extent to which surrogate measures of insulin release have shared genetic causes. METHODS: Genetic and phenotypic correlations were calculated in a family cohort (n = 315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma...... glucose, serum C-peptide and serum insulin levels. Furthermore, we genotyped a large population-based cohort (n = 6,269) for common genetic variants known to associate with type 2 diabetes, fasting plasma glucose levels or fasting serum insulin levels to examine their association with various indices....... RESULTS: We found a notable difference between the phenotypic and genetic correlations for the traits, emphasising that the phenotypic correlation is an insufficient measure of the magnitude of shared genetic impact. In addition, we found that corrected insulin response, insulinogenic index and inc...

  3. Association of the WFS1 gene with disease progression in children with new onset T1D. Results from the Hvidoere study group on childhood diabetes

    DEFF Research Database (Denmark)

    Nielsen, L.B.; Andersen, M.L.M.; Svensson, Jannete;

    2010-01-01

    variants the Wolfram syndrome. The aim of this study was to investigate the impact of a common genetic variant (rs10010131) of the WFS1 gene on disease progression in a group of children newly diagnosed with T1D. Methods: The study is a multicenter longitudinal investigation with 18 participating...... paediatric centres from 15 countries. Clinical information and blood samples were collected from 275 children less than 16 years at diagnosis and at 1, 6, and 12 months after onset. Genotyping of the rs10010131 variant was done by KBioscience using an in-house KASPar assay system. Statistics: C-peptide, HbA1......c, IDAA1c and proinsulin were analysed by multiple regression using age at onset, gender, DKA at onset, HLA class II risk groups, and genotypes as explanatory factors in a compound symmetric repeated measurement model. Results: The genotype frequencies were: 17% (AA), 48% (AG), 35% (GG), where the G...

  4. Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Khosla P

    1994-01-01

    Full Text Available Thirty-five patients of insulin-dependent diabetes mellitus (IDDM were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI levels and serum C-peptide radioimmunoreactivity (CPR as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM

  5. Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

    DEFF Research Database (Denmark)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-01-01

    CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. DESIGN......: The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion...... was measured. Cytokine concentrations in dialysate were also measured. RESULTS: Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P insulin, C-peptide, and glucagon were higher...

  6. Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently

    DEFF Research Database (Denmark)

    Ingerslev, Anne Krog; Theil, Peter Kappel; Hedemann, Mette Skou;

    2014-01-01

    adaptation to each diet. The pigs were fed a low DF western style control diet (WSD) and two high DF diets; an arabinoxylan (AXD) and a resistant starch (RSD) enriched diet. The NPF of insulin was lower (P = 0.04) in AXD fed pigs (4.6 nmol/h) compared to RSD fed pigs (10.5 nmol/h), despite the lowest NPF......The effects of increased colonic fermentation of dietary fibres (DF) on net portal flux (NPF) of carbohydrate-derived metabolites (glucose, SCFA and especially butyrate), hormones (insulin, C-peptide, GLP-1, GIP) and NEFA were studied in a healthy catheterised pig model. Six 59 ± 3.8 kg pigs were...... of glucose was observed in RSD fed pigs (203 mmol/h, P = 0.02). The NPF of total SCFA, acetate, propionate, and butyrate were high, intermediate, and low (P

  7. Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue

    International Nuclear Information System (INIS)

    Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients

  8. Comparison of the metabolic effects of recombinant human insulin-like growth factor-I and insulin. Dose-response relationships in healthy young and middle-aged adults.

    OpenAIRE

    Boulware, S. D.; Tamborlane, W V; Rennert, N J; Gesundheit, N; Sherwin, R S

    1994-01-01

    The actions of recombinant human insulin-like growth factor-I (rhIGF-I) and insulin were compared in 21 healthy young (24 +/- 1 yr) and 14 healthy middle-aged (48 +/- 2 yr) subjects during 3-h paired euglycemic clamp studies using one of three doses (rhIGF-I 0.2, 0.4, and 0.8 micrograms/kg.min and insulin 0.2, 0.4, and 0.8 mU/kg.min, doses chosen to produce equivalent increases in glucose uptake). In younger subjects, rhIGF-I infusions suppressed insulin by 19-33%, C-peptide by 47-59% and glu...

  9. Metabolism and pharmacokinetic of cyclo-peptides and peptides. Use of radioelement and stable isotopes

    International Nuclear Information System (INIS)

    More and more peptides and proteins are used in therapeutic. Three mainly techniques are used for pharmacokinetic and metabolism studies: immunoassay, radioactively labeled molecules and mass spectrometry. In the first part of this work, we have used uniformly labelled peptides (C-peptide and insulin) with stables (13C, 15N, and 13C/15N) or radioactive (14C) isotopes to investigated these kind of studies. These works are based on isotope dilution mass spectrometry assay. In a second time we have investigated the metabolism of a particular cyclo-peptides families composed of two amino acids: the diketo-piperazine. These compounds are found in mammals and in microorganisms. There are not recognized by proteolytic enzymes. We have estimated if the main enzymes implicated in the metabolism of xenobiotics, the P450 cytochrome mono-oxygenases, were able to recognized them

  10. Atrial natriuretic peptide, copeptin and adrenomedullin levels in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Frøssing, Signe; Nylander, Malin; Aziz, Mubeena;

    2016-01-01

    BACKGROUND: Polycystic ovary syndrome (PCOS) defined by the Rotterdam criteria does not take into account the unhealthy metabolic profile of the syndrome with increased insulin resistance (IR) and overweight favoring development of type 2 diabetes, hypertension and cardiovascular disease (CVD). We...... assess three vasoactive peptides associated with CVD in women with PCOS. METHOD: Plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin and mid-regional pro-adrenomedullin (MR-proADM) were measured in 98 PCOS patients and 46 age- and BMI-matched healthy women. RESULTS: We...... found no difference in levels of MR-proANP, copeptin and MR-proADM between the PCOS and control group. Multiple regression analyses on a combined group of PCOS and control subjects demonstrated an inverse correlation between MR-proANP and IR (measured by fasting C-peptide) and a positive correlations...

  11. Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients

    DEFF Research Database (Denmark)

    Sonne, David P; Hare, Kristine J; Martens, Pernille;

    2013-01-01

    Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We...... examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat......-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum...

  12. Inflammation as a Therapeutic Target for Diabetic Neuropathies.

    Science.gov (United States)

    Pop-Busui, Rodica; Ang, Lynn; Holmes, Crystal; Gallagher, Katherine; Feldman, Eva L

    2016-03-01

    Diabetic neuropathies (DNs) are one of the most prevalent chronic complications of diabetes and a major cause of disability, high mortality, and poor quality of life. Given the complex anatomy of the peripheral nervous system and types of fiber dysfunction, DNs have a wide spectrum of clinical manifestations. The treatment of DNs continues to be challenging, likely due to the complex pathogenesis that involves an array of systemic and cellular imbalances in glucose and lipids metabolism. These lead to the activation of various biochemical pathways, including increased oxidative/nitrosative stress, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage, cyclooxygenase-2 activation, endothelial dysfunction, altered Na(+)/K(+)-ATPase pump function, impaired C-peptide-related signaling pathways, endoplasmic reticulum stress, and low-grade inflammation. This review summarizes current evidence regarding the role of low-grade inflammation as a potential therapeutic target for DNs. PMID:26897744

  13. Residual β-Cell Function 3 to 6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

    DEFF Research Database (Denmark)

    Sorensen, Jesper Sand; Johannesen, Jesper; Pociot, Flemming;

    2013-01-01

    OBJECTIVETo determine the prevalence of residual -cell function (RBF) in children after 3-6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173...... boys) 4.8-18.9 years of age with type 1 diabetes for 3-6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA(1c), and daily insulin requirements was retrieved from the medical records....../mol]; P 0.2 nmol/L (mean +/- SE: 1.07 +/- 0.02 vs. 0.93 +/- 0.07 units/kg/day; P diabetes. Children with RBF...

  14. Human amnion epithelial cells can be induced to differentiate into functional insulin-producing cells

    Institute of Scientific and Technical Information of China (English)

    Yanan Hou; Qin Huang; Tianjin Liu; Lihe Guo

    2008-01-01

    Pancreatic islet transplantation has demonstrated that long-term insulin independence may be achieved in patients suffering from diabetes mellitus type 1. However, limited availability of islet tissue means that new sources of insulinproducing cells that are responsive to glucose are required. Here, we show that human amnion epithelial cells (HAEC) can be induced to differentiate into functional insulinproducing cells in vitro. After induction of differentiation, HAEC expressed multiple pancreatic --cell genes, including insulin, pancreas duodenum homeobox-1, paired box gene 6,NK2 transcription factor-related locus 2, Islet 1, glucokinase,and glucose transporter-2, and released C-peptide in a glucose-regulated manner in response to other extracellular stimulations. The transplantation of induced HAEC into streptozotocin-induced diabetic C57 mice reversed hyperglycemia, restored body weight, and maintained euglycemia for 30 d. These findings indicated that HAEC may be a new source for cell replacement therapy in type 1 diabetes.

  15. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion

    DEFF Research Database (Denmark)

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto;

    2009-01-01

    stimuli. RESEARCH DESIGN AND METHODS: We genotyped 1,578 nondiabetic subjects at increased risk of type 2 diabetes for rs151290, rs2237892, rs2237895, and rs2237897. All participants underwent an oral glucose tolerance test (OGTT); glucagon-like peptide (GLP)-1 and gastric inhibitory peptide secretion...... and basal or stimulated incretin levels (all P > or = 0.05). CONCLUSIONS: Common genetic variation in KCNQ1 is associated with insulin secretion upon oral glucose load in a German population at increased risk of type 2 diabetes. The discrepancy between orally and intravenously administered glucose seems...... C-peptide levels during OGTT, first-phase insulin secretion, and insulinogenic index after adjustment in the dominant model (all P indexes (all P

  16. The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Gethmann, Arnica; Nauck, Michael A;

    2006-01-01

    Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7-36) amide is degraded to the metabolite GLP-1-(9-36) amide. The effects of GLP-1-(9-36) amide in humans are less well characterized. Fourteen...... healthy volunteers were studied with intravenous infusion of GLP-1-(7-36) amide, GLP-1-(9-36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements......-(7-36) amide administration]. GLP-1-(7-36) amide reduced fasting and postprandial glucose concentrations (P gastric emptying (P

  17. alpha-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7-36 amide) and to delay gastric emptying in Type 2 diabetic patients

    DEFF Research Database (Denmark)

    Hücking, K; Kostic, Z; Pox, C;

    2005-01-01

    AIM: Acarbose is able to enhance GLP-1 release and delay gastric emptying in normal subjects. The effect of alpha-glucosidase inhibition on GLP-1 has been less evident in Type 2 diabetic patients. The aim of this study was to investigate the possible influence of acarbose on GLP-1 release...... and gastric emptying in Type 2 diabetic patients after a mixed test meal. PATIENTS AND METHODS: Ten Type 2 diabetic patients were tested with 100 mg acarbose or placebo served with a mixed meal that was labelled with 100 mg 13C-octanoic acid. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP......-1 and GIP were determined over 6 h. Gastric emptying was measured by determining breath 13CO2 using infrared absorptiometry. Statistics repeated-measures anova. RESULTS: Gastric emptying rates (t1/2: 162 +/- 45 vs. 163 +/- 62 min, P = 0.65) and plasma concentrations (increasing from approximately 12...

  18. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Meier, Juris J; Gallwitz, Baptist; Salmen, Stefan;

    2003-01-01

    The effects of different i.v. doses of glucagon-like peptide 1 (GLP-1) on glucose homeostasis and gastric emptying were compared in patients with type 2 diabetes. Twelve patients with type 2 diabetes received three different infusion rates of GLP-1 (0.4, 0.8, and 1.2 pmol/kg x min) or placebo...... in the fasting state and after a solid test meal (containing [(13)C]octanoic acid). Blood was drawn for glucose, insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate was calculated from the (13)CO(2) excretion rates in breath samples. Statistics were determined using repeated...... ingestion (P = 0.0031 and 0.0074, respectively). Glucagon secretion was suppressed with GLP-1. Gastric emptying was decelerated by GLP-1 in a dose-dependent fashion (P

  19. Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Hansen, Dorte L; Madsbad, Sten;

    2010-01-01

    OBJECTIVE: To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism. RESEARCH DESIGN AND METHODS: A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day...... into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured. RESULTS: Peroral feeding reduced 2-h postprandial plasma glucose (7.8 vs. 11.1 mmol/l) and incremental area under the glucose curve (i......AUC) (0.33 vs. 0.49 mmol . l(-1) . min(-1)) compared with gastroduodenal feeding. beta-Cell function (iAUC(Cpeptide/Glu)) was more than twofold improved during peroral feeding, and the glucagon-like peptide (GLP)-1 response increased nearly fivefold. CONCLUSIONS: Improvement in postprandial glucose...

  20. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vilsbøll, T; Krarup, T; Sonne, J;

    2003-01-01

    in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. Plasma concentrations of incretin hormones (total, reflecting secretion and intact......, reflecting potential action) were measured during two meal tests (260 kcal and 520 kcal) in eight type 1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic patients, and eight obese healthy subjects. Both in diabetic patients and in healthy subjects, significant increases in GLP-1...... and GIP concentrations were seen after ingestion of both meals. The incretin responses were significantly higher in all groups after the large meal, compared with the small meal, with correspondingly higher C-peptide responses. Both type 1 and type 2 diabetic patients had normal GIP responses, compared...

  1. Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes

    DEFF Research Database (Denmark)

    Zander, M; Taskiran, M; Toft-Nielsen, M B;

    2001-01-01

    OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted...... this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally......) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2...

  2. Human insulin dynamics in women: a physiologically based model.

    Science.gov (United States)

    Weiss, Michael; Tura, Andrea; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2016-02-01

    Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake.

  3. Glycaemic effects of bread and marmalade in insulin-dependent diabetes.

    Science.gov (United States)

    Lean, M E; Tennison, B R; Williams, D R

    1985-03-01

    The glycaemic responses of 12 C-peptide negative insulin-dependent diabetics were studied following four breakfasts with different carbohydrate sources. Total energy content of the meals was the usual for each subject, carbohydrate supplying 55% and fat 32%. The meals comprised: wholemeal bread with margarine; white bread with margarine; marmalade made with sucrose, and cheddar cheese; and marmalade (22% of total energy) on wholemeal bread with margarine. The study demonstrated powerfully that there were no statistically significant or clinically relevant differences between the meals in post-prandial glucose peak elevation, or in incremental area under the blood glucose curve to 120 mins. On these grounds, sucrose, in amounts considered acceptable to the general population, need not be prohibited from diabetic diets.

  4. Efficacy of Controlled- Release Glipizide in Treatment of Type 2 Diabetes%格列吡嗪控释片治疗2型糖尿病

    Institute of Scientific and Technical Information of China (English)

    曾文琴; 盛宏光

    2001-01-01

    目的观察格列吡嗪控释片及速释片治疗2型糖尿病的疗效对照,评价格列吡嗪控释片,其为依从性良好的抗糖尿病药物。方法治疗组22例服用控释片,对照组20例服用速释片。两组均测试服用前后葡萄糖耐量、胰岛素、C肽及糖化血红蛋白。结果控释片及速释片均有较好的降糖效果,而控释片又不增加血胰岛素及C肽水平。结论控释片降糖作用安全可靠,又减少了高胰岛素血症的发生。%Objective To compare the results of controlled- release glipizide and immediate-re- lease glipizide in treating type 2 diabetes mellitus. Methods 22 patients took controlled-release glipi- zide as treating group, 20 took immediate-release glipizide as compared. The glucose tolerance, insulin, C- peptide and HbA1c were measured before and after treatment. Results Both of controlled-release glipizide and immediate-release glipizide had good results for controlling blood sugar, but controlled-re- lease glipizide did not increase insulin and C-peptide level. Conclusion The controlled-release glipizide had safe and reliable results for controlling blood sugar and decreasing insulin resistence.

  5. Chronic liquid nutrition intake induces obesity and considerable but reversible metabolic alterations in Wistar rats.

    Science.gov (United States)

    Mikuska, Livia; Vrabcova, Michaela; Tillinger, Andrej; Balaz, Miroslav; Ukropec, Jozef; Mravec, Boris

    2016-06-01

    We have previously described the development of substantial, but reversible obesity in Wistar rats fed with palatable liquid nutrition (Fresubin). In this study, we investigated changes in serum hormone levels, glycemia, fat mass, adipocyte size, and gene expression of adipokines and inflammatory markers in adipose tissue of Wistar rats fed by Fresubin (i) for 5 months, (ii) up to 90 days of age, or (iii) after 90 days of age to characterize metabolic alterations and their reversibility in rats fed with Fresubin. An intra-peritoneal glucose tolerance test was also performed to determine levels of serum leptin, adiponectin, insulin, and C-peptide in 2- and 4-month-old animals. In addition, mesenteric and epididymal adipose tissue weight, adipocyte diameter, and gene expression of pro- and anti-inflammatory adipokines and other markers were determined at the end of the study. Chronic Fresubin intake significantly increased adipocyte diameter, reduced glucose tolerance, and increased serum leptin, adiponectin, insulin, and C-peptide levels. Moreover, gene expression of leptin, adiponectin, CD68, and nuclear factor kappa B was significantly increased in mesenteric adipose tissue of Fresubin fed rats. Monocyte chemotactic protein 1 messenger RNA (mRNA) levels increased in mesenteric adipose tissue only in the group fed Fresubin during the entire experiment. In epididymal adipose tissue, fatty acid binding protein 4 mRNA levels were significantly increased in rats fed by Fresubin during adulthood. In conclusion, chronic Fresubin intake induced complex metabolic alterations in Wistar rats characteristic of metabolic syndrome. However, transition of rats from Fresubin to standard diet reversed these alterations. PMID:26939586

  6. Characteristics and Determinants of Partial Remission in Children with Type 1 Diabetes Using the Insulin-Dose-Adjusted A1C Definition

    Directory of Open Access Journals (Sweden)

    Aurore Pecheur

    2014-01-01

    Full Text Available To evaluate the characteristics and determinants of partial remission (PR in Belgian children with type 1 diabetes (T1D, we analyzed records of 242 children from our center. Clinical and biological features were collected at diagnosis and during follow-up. PR was defined using the insulin-dose-adjusted A1C definition. PR occurred in 56.2% of patients and lasted 9.2 months (0.5 to 56.6. 25.6% of patients entered T1D with DKA, which correlated with lower PR incidence (17.6% versus 82.3% when no DKA. In our population, lower A1C levels at diagnosis were associated with higher PR incidence and in young children (0–4 years initial A1C levels negatively correlated with longer PR. Early A1C levels were predictive of PR duration since 34% of patients had long PRs (>1 year when A1C levels were ≤6% after 3 months whereas incidence of long PR decreased with higher A1Cs. C-peptide levels were higher in patients entering PR and remained higher until 3 years after diagnosis. Initial antibody titers did not influence PR except for anti-IA2 titers that correlated with A1C levels after 2 years. Presence of 2 versus 1 anti-islet antibodies correlated with shorter PR. PR duration did not influence occurrence of severe hypoglycemia or diabetes-related complications but was associated with lower A1C levels after 18 months. We show that, at diagnosis of T1D, parameters associated with β-cell mass reserve (A1C, C-peptide, and DKA correlate with the occurrence of PR, which affects post-PR A1C levels. Further research is needed to determine the long-term significance of PR.

  7. Immunoisolated transplantation of purified langerhans islet cells in testis cortex of male rats for treatment of streptozotocin induced diabetes mellitus.

    Science.gov (United States)

    Farhangi, Ali; Norouzian, Dariush; Mehrabi, Mohammad Reza; Chiani, Mohsen; Saffari, Zahra; Farahnak, Maryam; Akbarzadeh, Azim

    2014-10-01

    The objective of this study is to induce experimental diabetes mellitus by streptozotocin in normal adult Wistar rats via comparison of changes in body weight, consumption of food, volume of water, urine and levels of glucose, insulin and C-peptide in serum, between normal and diabetic rats. Intra-venous injection of 60 mg/kg dose of streptozotocin in 250-300 g (75-90 days) adult Wistar rats makes pancreas swell and causes degeneration in Langerhans islet β-cells and induces experimental diabetes mellitus in 2-4 days. For a microscopic study of degeneration of Langerhans islet β-cells of diabetic rats, biopsy from pancreas tissue of diabetic and normal rats, staining and comparison between them, were done. In this process, after collagenase digestion of pancreas, islets were isolated, dissociated and identified by dithizone method and then with enzymatic procedure by DNase and trypsin, the islet cells changed into single cells and β-cells were identified by immune fluorescence method and then assayed by flow-cytometer. Donor tissue in each step of work was prepared from 38 adult male Wistar rats weighted 250-300 g (75-90 days). Transplantation was performed in rats after 2-4 weeks of diabetes induction. In this study, the levels of insulin, C-peptide and glucose in diabetic rats reached to normal range as compared to un-diabetic rats in 20 days after transplantation of islet cells. Transplantation was performed under the cortex of testis as immunoisolated place for islet cells transplantation. PMID:25298622

  8. In-vitro differentiation of rat peripheral blood monocytes into insulin-producing cells by rat pancreatic extract

    Directory of Open Access Journals (Sweden)

    Tanhaye Kalate Sabz F

    2011-07-01

    Full Text Available Background: Cell-therapy provides a promising alternative for the treatment of type 1 diabetes. Monocytes which have a reprogramming or differentiation potential and are more available than any other types of stem cells, have been recognized as candidates for such investigations. The aim of the present study was to evaluate the differentiation potential of rat peripheral blood monocytes into insulin-producing cells by the use of rat pancreatic extract (2 days after a 60% pancreatectomy. Methods: Rat peripheral blood monocytes were isolated and cultured. Adherent monocytes were induced to differentiate into programmable cells in RPMI supplemented by 10% FCS, β-mercaptoetanol, M-CSF and IL-3 for six days. The dedifferentiated cells were analyzed by invert microscopy. Cultures of Programmable Cells of Monocytic Origin (PCMOs were continued in RPMI, containing 10% FBS, pancreatic extract and 5 mmol/L glucose for 15 days. The medium was replaced every three days. At the end of the protocol, insulin and c-peptide excreted by the differentiated cells were tested by radioimmunoassay on days 6, 14, and 21. In order to verify insulin production in the cells, dithizone-staining, which is a method for insulin identification, was employed. Results: The results showed that the cells cultured in rat pancreatic extract secreted insulin and c-peptide relative to the control group. Dithizone-staining was positive in the aforesaid cells (P<0/05. Conclusion: The results of the current study showed that pancreatic extract treatment can differentiate rat peripheral blood monocytes into insulin-producing cells which can be regarded as a potential source for the treatment of diabetes.

  9. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

    Directory of Open Access Journals (Sweden)

    Vikash Chandra

    Full Text Available BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs to differentiate into functional islet like cell aggregates (ICAs. Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17 and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.

  10. Comparison of plasma levels of obesity-related biomarkers among Japanese populations in Tokyo, Japan, São Paulo, Brazil, and Hawaii, USA.

    Science.gov (United States)

    Iwasaki, Motoki; Le Marchand, Loïc; Franke, Adrian A; Hamada, Gerson Shigeaki; Miyajima, Nelson Tomio; Sharma, Sangita; Yamaji, Taiki; Tsugane, Shoichiro

    2016-01-01

    Although Japanese in Japan and the USA are high-risk populations for colorectal cancer, the prevalence of obesity, one of the established risk factors for this disease, is low in these populations compared with other high-risk populations. To understand this inconsistency, we compared plasma obesity-related biomarkers in cross-sectional studies carried out in Tokyo, São Paulo, and Hawaii. We measured plasma levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-3, C-peptide, adiponectin, leptin, tumor necrosis factor-α, and interleukin-6 by immunoassay and total C-reactive protein, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides using a clinical chemistry autoanalyzer. A total of 299 participants were included in the present analysis, comprising 142 Japanese in Tokyo, 79 Japanese Brazilians in São Paulo, and 78 Japanese Americans in Hawaii. We found significantly lower plasma levels of C-peptide and IGF-I in Japanese in Tokyo than in Japanese Americans, and lower levels of leptin and triglycerides and higher levels of adiponectin, IGFBP-3, and high-density lipoprotein cholesterol in Japanese in Tokyo than in the other two populations. We also observed a significantly higher plasma IGFBP-1 level in Japanese Brazilians, and lower plasma levels of total cholesterol and low-density lipoprotein in Japanese Americans than in the other two populations. We observed significant differences in obesity-related biomarkers between the three Japanese populations. If our results are confirmed, the risk of colorectal cancer predicted on the basis of these biomarkers would be lowest for Japanese in Tokyo, followed by Japanese Brazilians and Japanese Americans.

  11. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

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    Dib Sergio A

    2009-12-01

    Full Text Available Abstract Type 1A diabetes mellitus (T1ADM is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ. Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation.

  12. Hyperferritinemia is associated with insulin resistance and fatty liver in patients without iron overload.

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    Robert Brudevold

    Full Text Available OBJECTIVE: During the last 10 years we have experienced an increasing number of referrals due to hyperferritinemia. This is probably due to increased awareness of hereditary hemochromatosis, and the availability of a genetic test for this condition. Most of these referred patients were over-weight middle-aged men with elevated ferritin levels, but without the hemochromatosis-predisposing gene mutations. We evaluated the relationship between hyperferritinemia and the metabolic syndrome in 40 patients. METHODS: Forty consecutive patients referred for hyperferritinemia were investigated. The examination programme included medical history, clinical investigation and venous blood samples drawn after an overnight fast. This resulted in 34 patients with unexplained hyperferritinemia, which were further examined. Liver biopsy was successfully performed in 29 subjects. Liver iron stores were assessed morphologically, and by quantitative phlebotomy in 16 patients. RESULTS: The majority of the patients had markers of the metabolic syndrome, and 18 patients (52% fulfilled the IDF-criteria for the metabolic syndrome. Mean body mass index was elevated (28.8+/-4.2, mean diastolic blood pressure was 88.5+/-10.5 mmHg, and mean fasting insulin C-peptide 1498+/-539 pmol/l. Liver histology showed steatosis and nuclear glycogen inclusions in most patients (19 out of 29. Only four patients had increased iron stores by histology, of which two could be explained by alcohol consumption. Fourteen of 16 patients normalized ferritin levels after phlebotomy of a cumulative blood amount corresponding to normal iron stores. Ferritin levels were significantly related to insulin C-peptide level (p<0.002 and age (p<0.002. CONCLUSION: The present results suggest that liver steatosis and insulin resistance but not increased iron load is frequently seen in patients referred for suspected hemochromatosis on the basis of hyperferritinemia. The ferritin level seems to be positively

  13. Pancreatic autoantibodies after pancreas-kidney transplantation - do they matter?

    Science.gov (United States)

    Martins, La Salete; Henriques, Antonio C; Fonseca, Isabel M; Rodrigues, Anabela S; Oliverira, José C; Dores, Jorge M; Dias, Leonidio S; Cabrita, Antonio M; Silva, José D; Noronha, Irene L

    2014-04-01

    Type 1 diabetes recurrence has been documented in simultaneous pancreas-kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow-up (maximum 138 months), 43.8% of patients were positive (from pre-transplant or after recurrence) for at least one autoantibody - the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti-insulin (8.6%) and anti-islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C-peptide levels, and a higher number of HLA-matches. Analyzing the sample divided into four groups according to pre-/post-transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C-peptide levels. Positivity for these autoantibodies pre-transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody-positive SPKT is a matter of concern, which deserves further attention.

  14. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation.

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    Volkert A L Huurman

    Full Text Available BACKGROUND: Islet cell transplantation can cure type 1 diabetes (T1D, but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG induction and tacrolimus plus mycophenolate mofetil (MMF maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively. Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome. CONCLUSIONS/SIGNIFICANCE: In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG

  15. Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of latent autoimmune diabetes in adults

    Institute of Scientific and Technical Information of China (English)

    李霞; 杨琳; 周智广; 黄干; 颜湘

    2003-01-01

    Objective To compare the clinical characteristics between type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) with different titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two distinct subtypes of LADA.Methods Sera of 750 patients with an initial diagnosis of T2DM from central south of China were screened for GADA using a radioligand assay. The distribution and frequency of GADA levels were described. Two hundred and ninety-five patients were divided into the T2DM group (n=233) and the LADA group (n=62) to compare the age of onset, body mass index, HbA1c, C-peptide, hypertension, dyslipidemia and chronic diabetic complications. Furthermore, LADA patients with different GADA titers were subdivided to analyze the same indexes as the above. Results The prevalence of LADA (defined as GADA≥0.05, namely GADA positive) was 9.7% in the 750 initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients were younger at their ages of onset, had lower C-peptide and body mass index, and also had less cases with hypertension and with dyslipidemia. However, only patients with high titer of GADA had poorer beta cell functions and less diabetic complications compared to T2DM and low GADA titer of LADA patients. Patients with low GADA titer were similar to T2DM patients, except that they were prone to develop ketosis more frequently.Conclusions Two clinically distinct subtypes of LADA can be identified by GADA levels in patients initially-diagnosed as type 2 diabetes. Patients with high titer of GADA (GADA≥0.5) subsequently develop more insulin dependency, which are classified as LADA-type 1; while those with lower GADA titer (0.05≤GADA<0.5) and having clinical and metabolic phenotypes of type 2 diabetes are classified as LADA-type 2.

  16. Effects of prolonged exposure to hypobaric hypoxia on oxidative stress, inflammation and gluco-insular regulation: the not-so-sweet price for good regulation.

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    Mario Siervo

    Full Text Available OBJECTIVES: The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses. METHODS: After baseline testing in London (75 m, 24 subjects ascended from Kathmandu (1,300 m to Everest Base Camp (EBC;5,300 m over 13 days. Of these, 14 ascended higher, with 8 reaching the summit (8,848 m. Assessments were conducted at baseline, during ascent to EBC, and 1, 6 and 8 week(s thereafter. Changes in body weight and indices of gluco-insular control were measured (glucose, insulin, C-Peptide, homeostasis model assessment of insulin resistance [HOMA-IR] along with biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE, inflammation (Interleukin-6 [IL-6] and counter-regulatory hormones (glucagon, adrenalin, noradrenalin. In addition, peripheral oxygen saturation (SpO2 and venous blood lactate concentrations were determined. RESULTS: SpO2 fell significantly from 98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained stable, insulin and C-Peptide concentrations increased by >200% during the last 2 weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with increases in markers of oxidative stress (4-HNE and inflammation (IL-6. Lactate levels progressively increased during ascent and remained significantly elevated until week 8. Subjects lost on average 7.3 kg in body weight. CONCLUSIONS: Sustained hypoxemia is associated with insulin resistance, whose magnitude correlates with the degree of oxidative stress and inflammation. The role of 4-HNE and IL-6 as key players in modifying the association between sustained hypoxia and insulin resistance merits further investigation.

  17. Screening of soy protein-derived hypotriglyceridemic di-peptides in vitro and in vivo

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    Matsui Toshiro

    2011-05-01

    Full Text Available Abstract Background Soy protein and soy peptides have attracted considerable attention because of their potentially beneficial biological properties, including antihypertensive, anticarcinogenic, and hypolipidemic effects. Although soy protein isolate contains several bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear which peptide sequences are responsible for the triglyceride (TG-lowering effects. In the present study, we investigated the effects of soy protein-derived peptides on lipid metabolism, especially TG metabolism, in HepG2 cells and obese Otsuka Long-Evans Tokushima fatty (OLETF rats. Results In the first experiment, we found that soy crude peptide (SCP-LD3, which was prepared by hydrolyze of soy protein isolate with endo-type protease, showed hypolipidemic effects in HepG2 cells and OLETF rats. In the second experiment, we found that hydrophilic fraction, separated from SCP-LD3 with hydrophobic synthetic absorbent, revealed lipid-lowering effects in HepG2 cells and OLETF rats. In the third experiment, we found that Fraction-C (Frc-C peptides, fractionated from hydrophilic peptides by gel permeation chromatography-high performance liquid chromatography, significantly reduced TG synthesis and apolipoprotein B (apoB secretion in HepG2 cells. In the fourth experiment, we found that the fraction with 0.1% trifluoroacetic acid, isolated from Frc-C peptides by octadecylsilyl column chromatography, showed hypolipidemic effects in HepG2 cells. In the final experiment, we found that 3 di-peptides, Lys-Ala, Val-Lys, and Ser-Tyr, reduced TG synthesis, and Ser-Tyr additionally reduced apoB secretion in HepG2 cells. Conclusion Novel active peptides with TG-lowering effects from soy protein have been isolated.

  18. Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabetes and in Arab control subjects. Ninety-two patients (65 females and 27 males) with type 2 diabetes and 69 matched normal and control subjects (48 females and 21 males) were included. Anthropometric measures (including body mass index (BMI) and waist: hip ratio) were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters include glucose, insulin, C-peptide, intact proinsulin, insulin resistance index (HOMA-IR), insulin-like growth factor 1 (IGF-1), lipids and hemoglobin A 1c (HbA) were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein (HDL) cholesterol were similar in patients with type 2 diabetes and control subjects. When obese subjects (BMI>-30kg/m2) were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA, and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BM, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low. (author)

  19. The preparation of monoclonal antibodies against human proinsulin and the development of immunoradiometric assay

    International Nuclear Information System (INIS)

    To prepare monoclonal antibodies against human proinsulin (hPI) and to develop a sensitive and specific two-site immunoradiometric assay for human proinsulin. Monoclonal antibodies (McAbs) against human hPi were prepared by the routine method. Two of these McAbs were selected to develop a sensitive and specific two-site IRMA for serum hPI. We used this assay to measure the fasting and postprandial serum concentrations of PI in healthy subjects, patients with NIDDM and those with insulinoma. We obtained 4 mouse McAbs (2A6, 4A2, 4E10, 4H9) against hPI. McAb 4H9 probably binds to an epitope that is located at the junction of A chain or B chain of insulin with c-peptide and the three others bind to epitopes that are located on the A chain or B chain of insulin. The detection limit of the IRMA for hPI was 1.9 pmol/L and the assay showed no cross-reaction with insulin and C-peptide. The mean fasting concentrations of PI was 5.5 +- 3.3 pmol/L and increased to 17.3 +-6.4 pmol/L one hour after a glucose loading in healthy subjects. They were 9.4% +- 1.5 pmol/L and 31.8 +- 9.4 pmol/L in patients with NIDDM. In a patient with insulinoma, the fasting concentration of PI was 106 pmol/L and 57 pmol/L before and one week after operation respectively. Based on the hPI specific McAbs produced in our laboratory, we developed a sensitive and specific two-site IRMA for serum hPI. It will be useful in the diagnosis of insulinoma and in the elucidation of the physiological and pathophysiological significance of PI in human

  20. NMR and photo-CIDNP studies of human proinsulin and prohormone processing intermediates with application to endopeptidase recognition

    International Nuclear Information System (INIS)

    The proinsulin-insulin system provides a general model for the proteolytic processing of polypeptide hormones. Two proinsulin-specific endopeptidases have been defined, a type I activity that cleaves the B-chain/C-peptide junction (Arg31-Arg32) and a type II activity that cleaves the C-peptide/A-chain junction (Lys64-Arg65). These endopeptidases are specific for their respective dibasic target sites; not all such dibasic sites are cleaved, however, and studies of mutant proinsulins have demonstrated that additional sequence or structural features are involved in determining substrate specificity. To define structural elements required for endopeptidase recognition, the authors have undertaken comparative 1H NMR and photochemical dynamic nuclear polarization (photo-CIDNP) studies of human proinsulin, insulin, and split proinsulin analogues as models or prohormone processing intermediates. The overall conformation of proinsulin is observed to be similar to that of insulin, and the connecting peptide is largely unstructured. In the 1H NMR spectrum of proinsulin significant variation is observed in the line widths of insulin-specific amide resonances, reflecting exchange among conformational substrates; similar exchange is observed in insulin and is not damped by the connecting peptide. The aromatic 1H NMR resonances of proinsulin are assigned by analogy to the spectrum of insulin, and assignments are verified by chemical modification. These results suggest that a stable local structure is formed at the CA junction, which influences insulin-specific packing interactions. They propose that this structure (designated the CA knuckle) provides a recognition element for type II proinsulin endopeptidase

  1. NMR and photo-CIDNP studies of human proinsulin and prohormone processing intermediates with application to endopeptidase recognition

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.A. (Harvard Medical School, Boston, MA (USA) Massachusetts General Hospital, Boston (USA)); Frank, B.H.; Heiney, R.; Pekar, A. (Eli Lilly and Co., Indianapolis, IN (USA)); Khait, I.; Neuringer, L.J. (Massachusetts Institute of Technology, Cambridge (USA)); Shoelson, S.E. (Harvard Medical School, Boston (USA))

    1990-09-11

    The proinsulin-insulin system provides a general model for the proteolytic processing of polypeptide hormones. Two proinsulin-specific endopeptidases have been defined, a type I activity that cleaves the B-chain/C-peptide junction (Arg{sup 31}-Arg{sup 32}) and a type II activity that cleaves the C-peptide/A-chain junction (Lys{sup 64}-Arg{sup 65}). These endopeptidases are specific for their respective dibasic target sites; not all such dibasic sites are cleaved, however, and studies of mutant proinsulins have demonstrated that additional sequence or structural features are involved in determining substrate specificity. To define structural elements required for endopeptidase recognition, the authors have undertaken comparative {sup 1}H NMR and photochemical dynamic nuclear polarization (photo-CIDNP) studies of human proinsulin, insulin, and split proinsulin analogues as models or prohormone processing intermediates. The overall conformation of proinsulin is observed to be similar to that of insulin, and the connecting peptide is largely unstructured. In the {sup 1}H NMR spectrum of proinsulin significant variation is observed in the line widths of insulin-specific amide resonances, reflecting exchange among conformational substrates; similar exchange is observed in insulin and is not damped by the connecting peptide. The aromatic {sup 1}H NMR resonances of proinsulin are assigned by analogy to the spectrum of insulin, and assignments are verified by chemical modification. These results suggest that a stable local structure is formed at the CA junction, which influences insulin-specific packing interactions. They propose that this structure (designated the CA knuckle) provides a recognition element for type II proinsulin endopeptidase.

  2. Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men

    Directory of Open Access Journals (Sweden)

    A.F. Reis

    1998-12-01

    Full Text Available Low levels of sex hormone-binding globulin (SHBG are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years with normal glucose tolerance and body mass indexes (BMI ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P28 kg/m2, N = 8 and nonobese (BMI £25 kg/m2, N = 10 groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand.

  3. Postprandial plasma adiponectin response is reduced in prepubertal premature pubarche girls.

    Science.gov (United States)

    Larqué, Elvira; Gil-Campos, Mercedes; Villada, Isabel; Ramírez-Tortosa, M Carmen; Cañete, Ramón; Gil, Angel

    2010-09-01

    The association between premature pubarche (PP) and metabolic syndrome is controversial and not supported by some authors. The aim of this study was to determine insulin resistance syndrome, plasma adiponectin, and fatty acid profile in PP girls to discern potential confounder variables and markers of metabolic disturbances. We studied 22 prepubertal girls with a diagnosis of PP and 20 healthy controls who differed in body mass index (BMI) (19.33 +/- 0.71 vs 17.30 +/- 0.60). We evaluated insulin resistance syndrome components and postprandial response of adiponectin, nonesterified fatty acids, and fatty acid profile after consumption of a standardized breakfast. No lipid disturbances were detected in the PP group. High-density lipoprotein to low-density lipoprotein cholesterol ratio tended to be lower in PP girls (P = .052), but this effect disappeared when data were adjusted for both BMI and age (P = .480). Insulin levels tended to be higher at 2 hours in PP girls, who showed significantly higher C-peptide area under the curve. In contrast, adiponectin at 3 hours after the meal and postprandial adiponectin area under the curve were significantly lower. The PP girls showed significantly higher percentages of eicosapentaenoic acid in total plasma and plasma phospholipids. No differences were found in the postprandial fatty acid clearance rate. In conclusion, PP girls and controls differed in postprandial plasma adiponectin response and in postprandial plasma C-peptide response after both BMI and age adjustment. Cholesterol plasma disturbances were mainly attributable to their higher BMI, although n-3 polyunsaturated fatty acids were higher because of the PP. PMID:20096425

  4. Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study

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    Anil Bhansali

    2014-01-01

    Full Text Available Background: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT through targeted approach in Type 2 Diabetes Mellitus.This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. Materials and Methods: Ten patients (8 men and 2 women with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day, metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders, while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL at the end of 15 months. Results: Six patients (60% were ′responders′ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ′responders′ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03, accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03, Homeostasis Model Assessment -β (P = 0.03 and QOL scores. However, ′non-responders′ did not show any significant alterations in these parameters. No serious adverse events were noted. Conclusion: Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.

  5. Voluntary wheel-running attenuates insulin and weight gain and affects anxiety-like behaviors in C57BL6/J mice exposed to a high-fat diet.

    Science.gov (United States)

    Hicks, Jasmin A; Hatzidis, Aikaterini; Arruda, Nicole L; Gelineau, Rachel R; De Pina, Isabella Monteiro; Adams, Kenneth W; Seggio, Joseph A

    2016-09-01

    It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed. PMID:27154535

  6. Hormonal Responses to Cholinergic Input Are Different in Humans with and without Type 2 Diabetes Mellitus

    Science.gov (United States)

    Dunai, Judit; Kilpatrick, Rachel; Oestricker, Lauren Z.; Wallendorf, Michael J.; Patterson, Bruce W.; Reeds, Dominic N.; Wice, Burton M.

    2016-01-01

    Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10), impaired glucose tolerance (IGT; n = 11), and type 2 diabetes mellitus (T2DM; n = 9). Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg) given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs) were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans. Trial Registration: ClinicalTrials.gov NCT01434901 PMID:27304975

  7. Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide.

    Science.gov (United States)

    Cardinale, Vincenzo; Puca, Rosa; Carpino, Guido; Scafetta, Gaia; Renzi, Anastasia; De Canio, Michele; Sicilia, Francesca; Nevi, Lorenzo; Casa, Domenico; Panetta, Rocco; Berloco, Pasquale Bartolomeo; Reid, Lola M; Federici, Giorgio; Gaudio, Eugenio; Maroder, Marella; Alvaro, Domenico

    2015-01-01

    Generation of β-pancreatic cells represents a major goal in research. The aim of this study was to explore a protein-based strategy to induce differentiation of human biliary tree stem cells (hBTSCs) towards β-pancreatic cells. A plasmid containing the sequence of the human pancreatic and duodenal homeobox 1 (PDX1) has been expressed in E. coli. Epithelial-Cell-Adhesion-Molecule positive hBTSCs or mature human hepatocyte cell line, HepG2, were grown in medium to which Pdx1 peptide was added. Differentiation toward pancreatic islet cells were evaluated by the expression of the β-cell transcription factors, Pdx1 and musculoapo-neurotic fibrosarcoma oncogene homolog A, and of the pancreatic hormones, insulin, glucagon, and somatostatin, investigated by real time polymerase chain reaction, western blot, light microscopy and immunofluorescence. C-peptide secretion in response to high glucose was also measured. Results indicated how purified Pdx1 protein corresponding to the primary structure of the human Pdx1 by mass spectroscopy was efficiently produced in bacteria, and transduced into hBTSCs. Pdx1 exposure triggered the expression of both intermediate and mature stage β-cell differentiation markers only in hBTSCs but not in HepG2 cell line. Furthermore, hBTSCs exposed to Pdx1 showed up-regulation of insulin, glucagon and somatostatin genes and formation of 3-dimensional islet-like structures intensely positive for insulin and glucagon. Finally, Pdx1-induced islet-like structures exhibited glucose-regulated C-peptide secretion. In conclusion, the human Pdx1 is highly effective in triggering hBTSC differentiation toward functional β-pancreatic cells. PMID:26252949

  8. Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide.

    Directory of Open Access Journals (Sweden)

    Vincenzo Cardinale

    Full Text Available Generation of β-pancreatic cells represents a major goal in research. The aim of this study was to explore a protein-based strategy to induce differentiation of human biliary tree stem cells (hBTSCs towards β-pancreatic cells. A plasmid containing the sequence of the human pancreatic and duodenal homeobox 1 (PDX1 has been expressed in E. coli. Epithelial-Cell-Adhesion-Molecule positive hBTSCs or mature human hepatocyte cell line, HepG2, were grown in medium to which Pdx1 peptide was added. Differentiation toward pancreatic islet cells were evaluated by the expression of the β-cell transcription factors, Pdx1 and musculoapo-neurotic fibrosarcoma oncogene homolog A, and of the pancreatic hormones, insulin, glucagon, and somatostatin, investigated by real time polymerase chain reaction, western blot, light microscopy and immunofluorescence. C-peptide secretion in response to high glucose was also measured. Results indicated how purified Pdx1 protein corresponding to the primary structure of the human Pdx1 by mass spectroscopy was efficiently produced in bacteria, and transduced into hBTSCs. Pdx1 exposure triggered the expression of both intermediate and mature stage β-cell differentiation markers only in hBTSCs but not in HepG2 cell line. Furthermore, hBTSCs exposed to Pdx1 showed up-regulation of insulin, glucagon and somatostatin genes and formation of 3-dimensional islet-like structures intensely positive for insulin and glucagon. Finally, Pdx1-induced islet-like structures exhibited glucose-regulated C-peptide secretion. In conclusion, the human Pdx1 is highly effective in triggering hBTSC differentiation toward functional β-pancreatic cells.

  9. Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism.

    Science.gov (United States)

    Higgins, Paul B; Rodriguez, Perla J; Voruganti, V Saroja; Mattern, Vicki; Bastarrachea, Raul A; Rice, Karen; Raabe, Timothy; Comuzzie, Anthony G

    2014-01-01

    Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry body composition scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, high-density lipoprotein, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ± 6.4 vs. 6.9 ± 4.0, P = 0.01). Although C-peptide, fasting glucose, and %HbA1c did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r = 0.61, P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.

  10. Does diabetes appear in distinct phenotypes in young people? Results of the diabetes mellitus incidence Cohort Registry (DiMelli.

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    Katharina Warncke

    Full Text Available INTRODUCTION: The diabetes mellitus Incidence Cohort Registry (DiMelli aims to characterize diabetes phenotypes by immunologic, metabolic, and genetic markers. We classified patients into three groups according to islet autoantibody status and examined whether patients with multiple diabetes-associated autoantibodies, one autoantibody, or without autoantibodies differed with respect to clinical, metabolic, and genetic parameters, including an insulin sensitivity (IS score based on waist, HbA1c, and triglycerides. We also assessed whether metabolic markers predicted the immune status. MATERIALS AND METHODS: As of June 2012, 630 patients in Bavaria, Germany, aged <20 years diagnosed with any type of diabetes within the preceding 6 months were registered in DiMelli. We compared the clinical and laboratory parameters between islet autoantibody status defined patient groups. Parameters showing the strongest associations were included in principal component analysis. Receiver operating characteristic curves were used to assess the ability of the IS Score to predict islet autoantibody status. RESULTS: Patients with multiple islet autoantibodies, one autoantibody, or without autoantibodies were significantly different in terms of BMI percentile, weight loss before diagnosis, fasting C-peptide (all, P<0.001, and IS Score (P=0.034. However, principal component analysis revealed no distinct patterns according to autoantibody status. At the optimal IS Score cut-off for predicting islet autoantibody positivity (single compared to none, the specificity was 52.0% and the sensitivity was 86.8%. With respect to prediction of multiple autoantibodies (compared to none, specificity and sensitivity were slightly lower and in combination inferior to those obtained using the BMI percentile and fasting C-peptide. DISCUSSION: The DiMelli study indicated that patients with and without islet autoantibodies differed with respect to metabolic and genetic markers but there

  11. 格列美脲联合甘精胰岛素治疗2型糖尿病的疗效%Efficacy of glimepiride in combination with insulin glargine in treating type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    公永明; 赵敏

    2011-01-01

    Objective; To observe the efficacy of glimepiride + insulin glargine in type 2 diabetes patients with secondary failure to sulfonylurea (SFS). Methods; Patients treated with glimepiride in combination with injection of insulin glargine (n =24) or Humulin 30R (n =30). The blood glucose, glycated hemoglobin (HbAlc) and serum C peptide were measured and compared at 12 weeks after treatment. Results; Both blood glucose and HbAlc were decreased (P<0.01 or <0. 05), and C peptide increased (P <0.05) after the two treatments. Conclusions; Treatment with glimepiride plus insulin glargine has satisfactory effect and may improve β cell function in patients with type 2 diabetes.%目的:观察磺脲类药物继发性失效者联合甘精胰岛素治疗2型糖尿病的疗效及胰岛β细胞功能变化.方法:对磺脲类药物继发性失效患者改用格列美脲,睡前分别注射甘精胰岛素(甘精组,24例)、优泌林30R(优泌林组,30例),12周后比较两组血糖、糖化血红蛋白(HbA1c)以及血清C肽的变化.结果:两组血糖和HbA1c均有下降(P<0.01或P<0.05),治疗后C肽升高(P<0.05).结论:联合甘精胰岛素治疗2型糖尿病有较好疗效,并有可能改善β细胞的功能.

  12. Study of Tripterygium Associated with Nicotinamide in Treating Late-onset Autoimmune Diabetes Mellitus in Adults

    Institute of Scientific and Technical Information of China (English)

    刘江华; 段世芳; 刘志文; 刘宗汉; 曹仁贤; 文芳; 文格波

    2004-01-01

    Objective: To explore the effect of Tripterygium polyglycoside (TP) associated with nicotinamide on the islet cell function, immune parameters and lipoperoxide (LPO) in adult patients with late-onset autoimmune diabetes mellitus (LADA) Methods: Thirty-six cases of LADA were randomly divided into three groups: TP group (n= 12), treated with TP plus orally taken metformin; combined treatment group (n =12), treated with TP combined with nicotinamide and metformin, and control group (n = 12) treated with metformin alone. They were followed-up for 18 months. Results: (1) Compared with the control group after 9months of treatment, postprandial plasma glucose and LPO in combined treatment group were decreased (P <0.05), and the postprandial C-peptide was higher (P<0.05). At the 18th month, the value of postprandial C-peptide in the TP and combined treatment group was higher than that in the control group. The slL-2R level of both TP and combined treatment groups were lowered (P<0.01); (2) Islet cell antibody (ICA) positive of 5 cases in the TP group and 6 cases in the combined treatment group got converted to the negative respectively, while only one in the control group at the time (P<0.05) ; (3) The level of LPO in the combined treatment group was significantly lower than that in the TP group at the 18th month of treatment (P<0.05).Conclusion: TP combined with nicotinamide played a role in immunity regulation, decreasing the titer of islet cell antibody and slL-2R, which also reduced the production of LPO and had a tendency to improve islet cell function in early LADA patients.

  13. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    Science.gov (United States)

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  14. A New Method for Local Dependence Map and Its Applications

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    Burcu H. ÜÇER

    2009-01-01

    Full Text Available Objective: This work introduces a new method to construct local dependence map based on the estimate for the linear local dependence function H(x,y, which is generalization of Pearson correlation coefficient. The new local dependence map demonstrates a practical tool for local dependence structure between two random variables. The analysis of theoretical concepts is verified by an application based on real datasets in endocrinology. Material and Methods: The method, local dependence map, requires the estimation new local dependence function which is based on regression concepts. After this local dependence function must be converted with local permutation tests in local dependence map which make the local dependence function more interpretable by identifying the regions of positive, negative and zero local dependence. Results: Based on the proposed method and we give two examples based on the real data C-peptide, insulin and TSH, FT3, FT4 from endocrinology in order to show the advantageous of the current dependence maps. They show interesting local dependence features on the other hand overall correlation coefficient is not much informative. Conclusion: Scalar dependence measures such as correlation coefficient are often used as a measure of dependence for data in medical and biological science. However, they cannot reflect the complex dependence structure of two variables. Hence we are now concerned exclusively with the statistical aspects of the dependence structure in dependence maps that will be constructed for the dataset. In this work a new method to construct local dependence map based on the regression concept for the linear local dependence function H(x,y, which is generalization of Pearson correlation coefficient, is established. The proposed new local dependence map is devoted to two examples based on the real data C-peptide, insulin and TSH, FT3, FT4 from endocrinology in order to illustrate the usefulness of the current dependence

  15. In Vivo Assessment of Antioxidants and Antihyperglycemic Effect of Barleria cristata leaves in Streptozotocin- Induced Diabetic Rats

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    Narmadha Rajasekaran

    2014-12-01

    Full Text Available Objective: Many new bioactive drugs isolated from plants having hypoglycaemic effects showed anti diabetic activity equal and sometimes even more potent than known oral hypoglycaemic agents. In this present study, designed to evaluate antihyperglycermic and antioxidants effect on ethanolic leaf extracts Barleria cristata (EtBc in streptozotocin-induced diabetic rats at dose level 400mg/kg body weight for the treatment of 45 days. Method and materials: The experimental rats were randomly divided into five groups as a control, streptozotocin induced with diabetes (45mg/kg bw without any treatment, treated with standard drug glibenclamide (1.25 mg/kg bw, EtBc (400 mg/kg bw in diabetic induced rats and treated with EtBc alone without diabetic rats. At the end of 45th day animals were sacrificed, collect the serum, liver, kidney and pancreas for estimate the glucose, insulin, C-peptide, glycosylated hemoglobin, hemoglobin in serum, protein, enzymatic and nonenzymatic antioxidants and lipid peroxidation in tissues. Results: After the administration of EtBc, blood glucose levels were showed significantly reduction (P<0.05 in diabetic rats and it has been observed alternation occured in body and organ weight and it was also normalized the serum level of glycemic profile like insulin, C-peptide, total hemoglobin and glycosylated hemoglobin levels similar to that of control rats. Antioxidants enzymes were return to back their levels as control in different tissues when compared to diabetic rats and also observed no significance difference between control and EtBc alone group rats at the end of 45th day. Therefore it was suggested that Barleria cristata may act by potentiation of pancreatic secretion of insulin or increasing glucose uptake by muscle cells. Conclusion: In this study, suggested the efficacy of Barleria cristata proved the maintenance of glucose homeostasis and may be used as a therapeutic agent in the management of diabetes mellitus.

  16. Obesidad y factores de riesgo del síndrome metabólico en jóvenes con diabetes tipo 1 Obesity and risk factors for metabolic syndrome in young people with type 1 diabetes

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    Mariana Prieto

    2012-08-01

    overlap of the two most common types of diabetes with a greater clinical heterogeneity. In order to characterize the type of diabetes at onset and assess the effect of obesity, 50 children with diabetes were studied. The patients were divided into two groups according to their nutritional status at diagnosis (overweight/obese vs. normal weight. Insulin reserve was evaluated by measuring basal C-peptide and stimulated C-peptide in response to a mixed meal (MMTT as well as HLA-DQB1 genotype, antibodies, and family history of risk factors for metabolic disease. Of all 50 patients, 38% was overweight /obese, 84% had a positive family history of metabolic syndrome, 82% had positive antibodies, and 100% were positive for the high-risk HLA-DQB1 genotype. No significant differences were found in fasting C-peptide or glycemic index/C-peptide levels between the two groups. In the overweight/obese group C-peptide response to MMTT showed higher levels at 60 and 120 minutes (p = 0.02 and 0.03 and the area under the curve for C-peptide was also higher (1.77 ng / ml vs. 5.5 ng/ml, p = 0.0007 than in the normal-weight group. In conclusion, overweight/obese patients with type 1A diabetes had a greater pancreatic reserve, suggesting that nutritional status may accelerate disease onset.

  17. 2型糖尿病700例低密度脂蛋白与并发症关系分析%Relationship of low density lipoprotein and diabetic complications in 700 patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    范丽; 杜新

    2013-01-01

    Objective To explore the control level of low density lipoprotein (LDL) in type 2 diabetes and know about the relationships between LDL and diabetic complications or indices. Methods This was a retrospective study in 700 patients with type 2 diabetes. Three groups were setted according to the control goal of blood lipids:A, LDL>2.6 mmol/L;B, 1.8 mmol/L≤LDL≤2.6 mmol/L;C, LDL<1.8 mmol/L. The differences were analysed between groups in intima-media thickness (IMT), HbA1c and function of islet cells, and chi-square test was done to compare the differences of prevalence in diabetic complications.The relationships between LDL, biochemical indices and diabetic complications were analysed through correlation analysis. Results The result showed 288 patients in group A, 274 in group B and 138 in group C. IMT, HbA1c, total cholesterol of groups A were significant higher than group B and C (P<0.05). Transcutaneous oxygen in group A was significant lower than B and C(P<0.05). C-peptide and 2 h C-peptide in group A were lower than B and C, but only C-peptide had statistics differences(P<0.05). No significant differences was found between three groups in prevalence of gender, diabetic retinopathy, diabetic peripheral neuropathy, diabetic nephropathy, cerebral infarction through chi-square test.The prevalence of coronary arterial disease was higher in group A than in B and C. LDL had positive correlations with IMT, HbA1c and negative correlations with C-peptide and 2 h C-peptide. Conclusion The disorder of lipids was associated with blood glucose level and function of islet cells. The prevalence of coronary arterial disease was high in diabetic patients with high LDL.%目的:探讨2型糖尿病患者低密度脂蛋白(LDL)控制水平,并进一步了解 LDL 与相关指标间以及糖尿病并发症间关系。方法回顾性分析700例2型糖尿病住院患者病历资料,根据血脂控制目标将所有患者分为三组:A,LDL>2.6 mmol/L;B,1.8 mmol

  18. Impact of subclinical hypothyroidism on metabolic risk factors of type 2 diabetes mellitus%亚临床甲状腺功能减退症对2型糖尿病代谢相关危险因素的影响

    Institute of Scientific and Technical Information of China (English)

    郭敏; 富强; 李毅; 杨远行

    2015-01-01

    Objective To compare and explore impact of subclinical hypothyroidism on metabolic risk factors of type 2 diabetes mellitus.Methods A total of 204 inpatients with type 2 diabetes mellitus.The patients were divide into two groups according to whether complicated with subclinical hypothyroidism:combination of simple type 2 diabetes mellitus (150 cases) and type 2 diabetes mellitus with SCH group(54 cases),two groups of age,gender,duration were no statistical difference.and collecting the clinical data of two groups of patients by Professional people,detection of blood lipids,glycated hemoglobin (HbA1c),uric acid (UA),Oral glucose tolerance test (OGTT),insulin and C peptide releasing test were taken in all groups.The improvement of insulin,C peptide index [HOMR-islet(CP)] and whole body insulin sensitivity index (ISIcomp) were used to estimate insuhn sensitivity,and improvement of insulin,C peptide secretion index [HOMR-isle (CP)] was used to evaluate the function of pancreatic islet β cell.T test was used for statistic alanalysis.Risk factors of type 2 diabetes mellitus with microvascular Complication by using Logistic regression analysis.Results (1) Compared with type 2 diabetes mellitus group,blood pressure,body mass index (BMI),triglycerides(TC),Low density lipoprotein cholesterol (LDL-C),UA,fasting C peptide(C-P0),postprandial 120 min C peptide(C-Pm),HOMA-IR(CP) were increased (P < 0.05),while fasting blood glucose(FPG),bloods glucose in postprandial 120 min (G120),HbA1c,ISI-comp were decreased (P < 0.05).(2) The incidence of diabetic nephropathy was higher in diabetic patents with subclinical hypothyroidism than those without subchnical hypothyroidism,the difference was statistically significant (P < 0.05).(3) Logistic analysis showed that duration,SBP,TSH were the major risk factors of type 2 diabetes mellitus with nephropathy (P < 0.05).Conclusions Type 2 diabetes mellitus patients with subclinical hypothyroidism compared to pure insulin resistance is

  19. The Impact of Diabetes on Serum Osteocalcin in Egyptian Children

    International Nuclear Information System (INIS)

    Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. Lack of diagnosis and treatment of alterations of the bone tissue metabolism in type1diabetes (T1D) may lead to osteoporosis.T1D most often starts before achieving peak bone mass.Recent studies have revealed that, in T1D fracture risk is increased more than expected from the degree of decrease in bone mineral density (BMD).Osteocalcin (OC) is considered a useful biochemical marker of bone formation. As in T1D, there is absolute insulin deficiency but insulin sensitivity remains generally intact. Therefore, this study was conducted to evaluate the association between OC levels in relation the degree of residual β-cell function and other metabolic parameters in T1D In the present study, the impact of diabetes on serum OC in Egyptian children and adolescents was evaluated by comparing serum level of OC in T1D (30 subjects) and age-matched non-diabetic control (15 subjects). The present study showed that, patients with T1D had lower OC serum levels compared to the controls (7.67 ± 3.55, 21.82 ± 4.96 μg/ml respectively, p < 0.001) with a lower OC levels in diabetic females than in diabetic males (5.92 ± 3.12, 8.74 ± 2.84 μg/ml respectively, p < 0.001) and lower OC levels in pre-pubertal than pubertal diabetic patients in both genders with p < 0.05. Serum OC levels in T1D correlated with HbAIc (p < 0.001), BMI (p < 0.05), durations of T1D (p < 0.05) and total daily insulin dose (p < 0.05)and did not correlate with C-peptide levels . It may be concluded that serum OC levels in patients with T1D are regulated by a variety of developmental and metabolic pathways. Since OC levels correlated with exogenous insulin(daily insulin dose) and did not correlate with endogenous insulin (C-peptide levels), therefore, it is presumed that OC was regulated by insulin-mediated events, in presence of aggressive autoimmune destruction of pancreatic cell. These results proposed that

  20. 妊娠期糖尿病胎儿代谢的相关研究%Related research on metabolism of fetuses with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陈小青; 蔡庆华

    2011-01-01

    目的:通过测定妊娠期糖尿病(GDM)脐血脂联素、胰岛素、C肽、糖化血红蛋白水平,探讨GDM对胎儿代谢水平的影响.方法:采用放射免疫法测定30例GDM患者及26例上正常孕妇脐血脂联素、胰岛素、C肽水平,采用乳胶增强的免疫竞争抑制法测定脐血糖化血红蛋白水平.结果:GDM组脐血脂联素水平为(20.74±5.66)μg/ml,明显低于对照组(26.66±8.43)μg/ml,脐血胰岛素、糖化血红蛋白水平分别为(31.53±14.63)uIU/ml,(4.9±0/7)%,明显高于对照组,差异有统计学意义.两组脐血脂联素水平与脐血胰岛素、糖化血红蛋白呈明显负相关.结论:宫内暴露于GDM不良环境因素下可引起胎儿脂联素水平的下降及胰岛素、C肽、糖化血红蛋白水平的升高.胎儿代谢水平的改变影响了胎儿的生长发育,还可能与将来子代的代谢性疾病具有相关性.%Objective: To explore the effect of gestational diabetes mellitus (GDM) on fetal metabolism level by detecting the levels of adiponectin, insulin, C -peptide and glycosylated hemoglobin in umbilical cord blood.Methods: Radioimmunoassay was used to detect the levels of adiponectin, insulin and C - peptide in umbilical cord blood of 30 cases with GDM and 26 normal pregnant women, latex enhanced immunosuppression competition method was used to detect the levelof glycosylated hemoglobin in umbilical cord blood.Results:The level of adiponectin in umbilical cord blood in GDM group was ( 20.74 ± 5.66 ) μg/ml, which was significantly lower than that in control group [(26.66 ± 8.43 ) μg/ml], the levels of insulin and glycosylated hemoglobin in umbilical cord blood in GDM group were (31.53 ±14.63 ) uIU/ml and (4.9 ± 0.7 )%, respectively, which were significantly higher than those in control group; there was negative correlation between adiponectin level and insulin, glycosylated hemoglobin levels in umbilical cord blood in the two groups.Conclusion: Exposure to bad environment

  1. Selection of pathogenic indicators in the early stage of diabetes rats%大鼠糖尿病模型早期病理观察指标的筛选

    Institute of Scientific and Technical Information of China (English)

    王洪敏; 钟志勇; 吴庆洲; 罗肇璋; 莫国玉; 杨富强; 饶桂荣; 杜桂容; 陈光明

    2011-01-01

    Objective To select the sensitive pathogenic and biochemical indicators in the early stage of diabetes rats , diabetes in SD rats was induced by intraperitoneal injection of Streptozotocin at different doses. Methods 60 SD rats were randomly divided into 6 groups,intraperitoneally injected with streptozotocin at the doses of 0,20 ,30,50 , and 80 mg/kg respectively. Fasting blood glucose level,random blood sugar level, and body weight were recorded daily from the second day of injection, pathological examinations of kidney, pancreas, eye ball,liver, spleen , lung, aorta,and testicles were conducted, and serum insulin levels and C-peptide were assayed in the 9th day after the beginning of injection. Results No significant difference of the pathogenic and biochemical indicators of rats from groups intraperitoneally injected with streptozotocin at 20 mg and 30 mg was observed;Fasting blood glucose level in the groups intraperitoneally injected with streptozotocin at 50 and 80 mg/kg increased significantly, onsets of lesions in kidney, eyeball, and pancreas in the rats were observed, and the number of islets decreased significantly ( P < 0. 05 ) . And serum insulinand C-peptide levels in the group of rats intraperitoneally injected with streptozotocin at 50 and 80 mg/kg also decreased significantly ( P < 0. 05 ).Conclusion In the early stage of diabetes mellitus, levels of fasting blood glucose, insulin, C-peptide, bodyweight,pancreas, kidney and eyes were key monitoring indicators. And no obvious changes of heart, liver,spleen,lung,aorta, and testicles in the rats in the early stage of diabetes were observed.%目的 通过腹腔注射链脲佐菌素(STZ)制作大鼠糖尿病模型,筛选成模早期对糖尿病变化敏感的器官组织及生化指标.方法 60只雄性SD大鼠随机分成5组,分别腹腔一次性注射0、20、30、50和80mg/kg的STZ,注射STZ后第2天开始检测各组大鼠的空腹血糖、随机血糖及体质量,第9天实验结束时,取

  2. Lispro 50 Newly Diagnosed Patients with Type 2 Diabetes Blood Sugar and Pancreaticβ-cell Function%赖脯胰岛素50对初诊2型糖尿病患者血糖及胰岛β细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    徐风梅; 赵霞

    2013-01-01

      目的:探究赖脯胰岛素50对初诊2型糖尿病血糖和胰岛β细胞功能的影响。方法:选取笔者所在医院内分泌科的住院初诊为2型糖尿病患者共122例,采用电脑的随机的方法,将受试对象随机分为常规组和赖脯组各61例,常规组用优泌林混合型、赖脯组用赖脯胰岛素50进行降糖治疗,测量两组患者治疗前后各项血糖和C肽相关指标的变化情况。结果:两组患者血糖都有良好的控制,相互没有差异;但常规组患者治疗前后C肽水平没有明显变化;赖脯组治疗前后C肽水平有明显变化,并且较常规组差异明显。结论:赖脯胰岛素50在有效控制血糖的同时,能更好地摸拟生理性胰岛素分泌,有助于胰岛β细胞功能的恢复。%Objective:To explore the lispro impact of 50 newly diagnosed with type 2 diabetes and isletβ-cell function.The hospital diagnosed as type 2 diabetes patients with a total of 122 cases in our hospital Endocrinology,using computer random.Method:The subjects were randomly divided into conventional group and lispro group of 61 cases,the conventional group Humulin hybrid lispro group hypoglycemic treatment with lispro 50,measuring the blood glucose and C-peptide index changes in the two groups of patients before and after treatment.Have good.Result:Of two groups of patients with blood glucose control,with each other there is no difference;regular group of patients before and after treatment the C-peptide levels did not change significantly;significant change in C-peptide levels in the lispro group before and after treatment,and the differences are significant compared to the conventional group.Conclusion:Lispro 50 while in the effective control of blood glucose,better simulated physiological insulin secretion,contribute to the recovery ofβ-cell function.

  3. 全胃切除消化道重建术对胃癌合并Ⅱ型糖尿病血糖的影响%Total gastrectomy reconstruction procedures on blood sugar of gastric cancer concomitance T2DM

    Institute of Scientific and Technical Information of China (English)

    汪启斌; 董荣坤; 张笃; 马芷琴

    2012-01-01

    目的 研究全胃切除加消化道重建术对胃癌合并Ⅱ型糖尿病(T2DM)术后血糖的影响.方法 将胃底贲门癌合并T2DM患者25例行全胃切除加Roux-Y吻合术(A组);选取同期的远端胃癌合并T2DM患者25例行毕Ⅱ式手术(B组)作为对照组;比较两组术后第一个月及丰年的血糖、C肽、糖化血红蛋白变化,采用t检验.结果 ①A组手术前后血糖、糖化血红蛋白及C肽改善无显著性差异(P>0.05),B组手术前后血糖、糖化血红蛋白及C肽的变化有显著性差异(P<0.05).②两组间术后对比差异有显著性(P<0.05).结论 ①全胃切除加Roux-Y吻合术对术后近期血糖无明星影响.②毕Ⅱ式术后近期血糖有明显改善,该术式对糖尿病有治疗作用.③胃与术后糖尿病改善有密切关系.④迷走神经肝支可能影响肠-胰岛轴.%Objective To explore the effect of total gastrectomy adding reconstruction procedures on blood sugar of gastric cancer concomitance T2DM. Methods 25 cases were operated total gastrectomy and Roux-Y on gastric bottom and cardia cancer consolidation type 2 diabetes mellitus (A group),at the same time,25 cases gastric sinuses cancer were performed Billioth 1KB group) ,to be collating group. To compare preoperative and postoperative the blood sugar. HbAlc and C peptide among A and B, using t test to analyze. Results 1. The difference was no significant that A group preoperative and postoperative the biood sugar, HbAlc and C peptide. The difference was significant that B group preoperative and postoperative the blood sugar, HbAlc and C peptide. 2. The postoperative difference was significant among A group and B. Conclusion The operation total gastrectomy adding Roux-Y don't evidently produce an effect on postoperative blood sugar in the near future. The operation Billroth II do evidently affect on postoperative blood sugar in the near future, it show that the operation can treat T2DM. 3. The relation of stomach and

  4. Pancreas transplantation: The Wake Forest experience in the new millennium

    Institute of Scientific and Technical Information of China (English)

    Jeffrey; Rogers; Alan; C; Farney; Giuseppe; Orlando; Samy; S; Iskandar; William; Doares; Michael; D; Gautreaux; Scott; Kaczmorski; Amber; Reeves-Daniel; Amudha; Palanisamy; Robert; J; Stratta

    2014-01-01

    AIM: To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. METHODS: A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant(SKPT) and solitary pancreas transplant(SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with my-cophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. RESULTS: Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186(92%) were primary and 16(8%) pancreas retransplants; portalenteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American(AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/m L. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit antithymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient(86% SKPT vs 87% SPT) and kidney(74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates(both 65%) were similar(P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively(P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and

  5. 甘精胰岛素联合格列美脲片治疗2型糖尿病的疗效观察%Efficacy of insulin glargine plus glimepiride for type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    谢彬; 熊晓清; 冉建民

    2010-01-01

    Objective To investigate the efficacy and safety of insulin glargine plus glimepiride in the treatment of type 2 diabetic patients. Methods Sixty patients poorly responsive to oral sulfonylureas were randomly assigned to receive oral glimepiride plus injections of either insulin glargine (GL group, 30 patients) or neural protamine hagedorn (NPH group, 30 patients) for 12 weeks. Levels of fasting blood glucose and C-peptide, postprandial blood glucose and C-peptide, and HbAlc were detected 12 weeks after treatment. Results The fasting and postprandial blood glucose levels were significantly decreased. The incidence of hypoglycemia was lower in GL group than in NPH group (P<0.05) and C-peptide level was markedly higher. Conclusions Combination therapy with insulin glargine and glimepiride for type 2 diabetes is safe, effective, simple, and feasible. It can reduce the incidence of hypoglycemia and improve pancreatic function.%目的 探讨甘精胰岛素联用格列美脲片治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性.方法 60例口服磺脲类降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组(GL组)和中性鱼精蛋白锌胰岛素(NPH)组,予睡前皮下注射胰岛素联合口服格列美脲治疗12周,观察12周前后空腹血糖、餐后2h血糖、糖化血红蛋白、空腹C肽、餐后C肽的变化.结果 GL组治疗后FPG(6.3±1.4)mmol/L,2hPG(8.7±1.4)mmol/L,HbAlc(6.7±0.61%;NPH组治疗后FPG(6.4±1.0)mol/L,2hPG(8.8 4±1.2)mmol/L,HbAlc(6.6±0.7)%,较治疗前差异有极显著性(P<0.01);但GL组的低血糖事件明显少于NPH组(P<0.05).且GL组治疗后C肽水平明显升高.结论 甘精胰岛素联用格列美脲片治疗2型糖尿病的方案安全有效,简便易行,能减少低血糖事件的发生,且可能改善胰岛功能.

  6. Objective and self-rated sedentary time and indicators of metabolic health in Dutch and Hungarian 10-12 year olds: the ENERGY-Project.

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    Mai J M Chinapaw

    Full Text Available BACKGROUND: The association between objectively assessed sedentary time and metabolic risk factors in childhood have rarely been studied. Therefore, we examined the independent relationship between objectively assessed and self-rated sedentary time and indicators of metabolic health in Dutch and Hungarian 10-12 year olds. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional survey in primary schools. Participants were Dutch and Hungarian girls (n = 73, aged 12.2 ± 0.6 years, 18% overweight/obese and boys (n = 69, aged 12.2 ± 0.7 years, 38% overweight/obese. Sedentary time and physical activity were assessed by the Actigraph accelerometer. TV and PC time were assessed by self-report. Adiposity indicators included body weight, height, and waist circumference (WC. Fasting plasma glucose, C-peptide, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were determined in capillary blood and summed into a metabolic risk score. Linear regression analyses were adjusted for physical activity, number of sedentary bouts and WC. Children spent on average 7.6 hours of their daily waking time in sedentary behavior and self-reported 116 ± 64 min/day watching TV and 85 ± 57 min/day using the computer. Comparing the 1(st and 4(th quartile of objectively assessed sedentary time, C-Peptide levels, WC and BMI were significantly higher in the most sedentary quartile, while the difference in metabolic risk score was borderline significant (p = 0.09. Comparing the 1(st and 4(th quartile of TV time, BMI was significantly higher in the most sedentary quartile, while the difference in WC score was borderline significant (p = 0.06. In the adjusted linear regression analysis we found no significant association of sedentary time with metabolic risk. CONCLUSIONS/SIGNIFICANCE: Although BMI and WC were higher in the most sedentary versus the least sedentary children; we found no further evidence that more

  7. Change of glutamic acid decarboxylase antibody and protein tyrosine phosphatase antibody in Chinese patients with acute-onset type 1 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    CHAO Chen; HUANG Gan; LI Xia; YANG Lin; LIN Jian; JIN Ping; LUO Shuo-ming

    2013-01-01

    Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies,which exert important roles in the process of type 1 diabetes mellitus (T1D).Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.Methods Two hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited.GADA and IA-2A were detected at the time of diagnosis,one year later,3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.Results During the course of acute-onset T1D,the majority of patients remained stable for GADA or IA-2A,however,a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity.The prevalence of GADA was 56.3% at diagnosis,decreasing to 50.5% one year later,and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%,31.0% and 23.3%,respectively.The median GADA titers were 0.0825 at diagnosis,declining to 0.0585 one year later and 0.0383 3-5 years later (P <0.001),while the corresponding median titers were 0.0016,0.0010,0.0014 for IA-2A,respectively.Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h)levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P <0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.Conclusion Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.

  8. The Relationship between Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Measured by Controlled Attenuation Parameter

    Science.gov (United States)

    Chon, Young Eun; Kim, Kwang Joon; Jung, Kyu Sik; Kim, Seung Up; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Chon, Chae Yoon; Chung, Jae Bock; Park, Kyeong Hye; Bae, Ji Cheol

    2016-01-01

    Purpose The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). Materials and Methods Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). Results Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21–6.64), and positive correlations between the CAP value and HOMA-IR (ρ=0.407) or fasting C-peptide (ρ=0.402) were demonstrated. Conclusion Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection. PMID:27189281

  9. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with alogliptin

    Directory of Open Access Journals (Sweden)

    Jurczyk A

    2013-12-01

    Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice

  10. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells

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    Zhao Yong

    2012-01-01

    Full Text Available Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D. Evidence that human cord blood-derived multipotent stem cells (CB-SCs can control autoimmune responses by altering regulatory T cells (Tregs and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15 with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41, and median diabetic history was 8 years (range: 1 to 21. Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6 and patients with no residual pancreatic islet β cell function (n = 6. Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3 did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS, increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell

  11. T he Effects of Olanzapine and Clozapine on Glucose M etabolism and Lipid M etabolism%精神分裂症患者口服奥氮平和氯氮平对糖及脂代谢的影响

    Institute of Scientific and Technical Information of China (English)

    苗淑芳

    2015-01-01

    Objective We study the side-effect of olanzapine and clozapine on theglucose metabolism and lipid metabolism in schizophrenic patients .Method 7 1 cases of hospitalized patients with schizophrenia(2 0 1 0 .3-2 0 1 0 .1 1 ) ,randomly divided into two groups were given clozapine and olanzapine treatment .Determination of Cholesterol ,triglyceride ,fasting glucose ,insulin and C peptides by Roche Modular P8 0 0 .Measured the height and weight to calculate body mass index .Determination of olanzapine ,clozapine and N -demethyl clozapine in plasma .Results Clozapine and olanzapine treatment for body mass index ,triglycerides ,insulin and c-peptide the influence of the difference was statistically significant(P0 .0 5 ) .Conclusion Clozapine and olanzapine have effect on glucose metabolism , lipid metabolism and body mass index ,but the influence of clozapine .We should pay attention to the changes of blood sugar and blood fat w hen using atypical psychotropic drugs in clinical practices .%目的:探讨精神分裂症患者服用奥氮平和氯氮平后对体重指数、糖代谢和脂代谢指标变化的影响。方法选取我院2010年3~11月71例住院精神分裂症患者,随机分成两组,分别给予氯氮平和奥氮平治疗。采用罗氏全自动生化分析仪检测患者的糖代谢和脂代谢指标以及测量患者身高、体重,计算体重指数。结果氯氮平和奥氮平治疗后对体重指数、甘油三脂、胰岛素和C肽的影响差异有统计学意义(P<0.05),对血糖的影响差异无统计学意义(P>0.05)。结论氯氮平与奥氮平对糖代谢、脂代谢和体重指数都有影响,但氯氮平影响相对较大,临床治疗过程中应注意监测糖脂代谢的变化。

  12. Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice

    Institute of Scientific and Technical Information of China (English)

    ZHI Min; WU Kai-chun; HAO Zhi-ming; GUO Chang-cun; YAO Jia-yin

    2011-01-01

    Background Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.Methods The phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced.During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues.Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and Ⅷ-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.Results The number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P <0.01 in tumor and spleen, P <0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or Ⅷ-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by

  13. The effect of Shenmai injection on elderly patients with type 2 diabetes islet function and circulation state

    Institute of Scientific and Technical Information of China (English)

    Shao-Sheng Tang

    2015-01-01

    Objective: To study effect of Shenmai injection on elderly patients with type 2 diabetes islet function and circulation state. Methods: Between January 2011 and September 2014, 60 cases of elderly patients with type 2 diabetes were selected as the research object, and 60 patients according to random number table method were randomly divided into observation group and control group with 30 cases each. Control group: 30 cases were given conventional western medicine treatment; Observation group: 30 cases were given Shenmai injection treatment based on the control group. 1 week, 3 weeks before and after treatment C peptide and insulin secretion index (HOMA beta), insulin resistance index (HOMA IR) and glycosylated hemoglobin (HbA1c), input branch pipe diameter, output, branch pipe diameter, loop of blood vessel diameter, number of loop deformity, pipe loop integral, zhou state points, such as flow, total integral index were tested. Results: 3 weeks, 1 week after treatment, serum c-peptide, HOMA beta levels in the observation group were obviously higher than the same period in the control group, and serum HOMA IR, HbA1c levels were significantly lower than the control group during this period, and the difference was statistically significant (P<0.05); 3 weeks, 1 week after treatment, in treatment group output input branch pipe diameter, branch pipe diameter, loop blood vessel diameter were significantly higher than control group during this period, and the number of loop deformity significantly was lower than the control group during this period, and the difference was statistically significant (P<0.05), and the difference was statistically significant (P<0.05); 3 weeks, 1 week after treatment, in treatment group pipe loop integral, zhou state, the flow integral and total integral were significantly lower than the control group during this period, and the difference was statistically significant (P<0.05). Conclusion:Using Shenmai injection in the treatment of type 2

  14. Antidiabetic Effects of Yam (Dioscorea batatas and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes

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    Hyeon-Kyu Go

    2015-10-01

    Full Text Available The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas powder (PY, water extract of yam (EY, and allantoin (the active constituent of yam in streptozotocin (STZ-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1, C-peptide, glycated hemoglobin (HbAlc, lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC, diabetic control (STZ, and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin. After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p < 0.001 compared to STZ (100%: 60% in STZ + PY, 55% in STZ + EY, and 63% in STZ + allantoin. With groups in the same order, there were significant decreases (p < 0.001 in HbAlc (100% as 24.4 ± 0.6 ng/mL, 78%, 75%, and 77%, total cholesterol (100% as 122 ± 3 mg/dL, 70%, 67%, and 69%, and low-density lipoprotein (100% as 29 ± 1 mg/dL, 45%, 48%, and 38%. There were also significant increases (p < 0.001 in insulin (100% as 0.22 ± 0.00 ng/mL, 173%, 209%, and 177%, GLP-1 (100% as 18.4 ± 0.7 pmol/mL, 160%, 166%, and 162%, and C-peptide (100% as 2.56 ± 0.10 ng/mL, 129%, 132%, and 130%. The treatment effectively ameliorated antioxidant stress as shown by a significant decrease (p < 0.001 in malondialdehyde (100% as 7.25 ± 0.11 nmol/mL, 87%, 86%, and 85% together with increases (p < 0.01 in superoxide dismutase (100% as 167 ± 6 IU/mL, 147%, 159%, and 145% and reduced glutathione (100% as 167 ± 6 nmol/mL, 123%, 141%, and 140%. The results indicate that yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose levels.

  15. Glucose-raising genetic variants in MADD and ADCY5 impair conversion of proinsulin to insulin.

    Directory of Open Access Journals (Sweden)

    Robert Wagner

    Full Text Available INTRODUCTION: Recent meta-analyses of genome-wide association studies revealed new genetic loci associated with fasting glycemia. For several of these loci, the mechanism of action in glucose homeostasis is unclear. The objective of the study was to establish metabolic phenotypes for these genetic variants to deliver clues to their pathomechanism. METHODS: In this cross-sectional study 1782 non-diabetic volunteers at increased risk for type 2 diabetes underwent an oral glucose tolerance test. Insulin, C-peptide and proinsulin were measured and genotyping was performed for 12 single nucleotide polymorphisms (SNP in or near the genes GCK (rs4607517, DGKB (rs2191349, GCKR (rs780094, ADCY5 (rs11708067, MADD (rs7944584, ADRA2A (rs10885122, FADS1 (rs174550, CRY2 (rs11605924, SLC2A2 (rs11920090, PROX1 (rs340874, GLIS3 (rs7034200 and C2CD4B (rs11071657. Parameters of insulin secretion (AUC Insulin(0-30/AUC Glucose(0-30, AUC C-peptide(0-120/AUC Glucose(0-120, proinsulin-to-insulin conversion (fasting proinsulin, fasting proinsulin/insulin, AUC Proinsulin(0-120/AUCInsulin(0-120 and insulin resistance (HOMA-IR, Matsuda-Index were assessed. RESULTS: After adjustment for confounding variables, the effect alleles of the ADCY5 and MADD SNPs were associated with an impaired proinsulin-to-insulin conversion (p = 0.002 and p = 0.0001, respectively. GLIS3 was nominally associated with impaired proinsulin-to-insulin conversion and insulin secretion. The diabetogenic alleles of DGKB and PROX1 were nominally associated with reduced insulin secretion. Nominally significant effects on insulin sensitivity could be found for MADD and PROX1. DISCUSSION: By examining parameters of glucose-stimulated proinsulin-to-insulin conversion during an OGTT, we show that the SNP in ADCY5 is implicated in defective proinsulin-to-insulin conversion. In addition, we confirmed previous findings on the role of a genetic variant in MADD on proinsulin-to-insulin conversion. These

  16. Related Factors Research of Diabetic Peripheral Neuropathy%糖尿病周围神经病变相关因素研究

    Institute of Scientific and Technical Information of China (English)

    吴卫国

    2012-01-01

    目的:探讨糖尿病周围神经病变(DPN)的相关发病因素.方法:回顾我院2006年1月~2012年2月期间收治的86例糖尿病患者的临床资料,所有患者均做空腹血糖(FPG)、餐后2h血糖(PBG)、总胆固醇(TC)、甘油三脂(TG)、空腹胰岛素(FINS)、餐后2h胰岛素(2hINS)、空腹C肽(FCP)、餐后2hC肽(2hCP)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)检查.结果:通过检查分析,病程、FPG、2hINS、FCP、2hCP、PBG、TG都有明显差异(P0.05),62例T1DM患者中出现28例DPN,24例T2DM糖尿病患者中出现7例DPN.结论:DPN的影响因素较多,年龄、病程是DPN的主要危险因素,较好的血糖控制,可以有效预防DPN的发生.%Objective:To study the diabetic peripheral neuropathy (DPN) of the related factors.Methods:To review 86 cases treated patients with diabetes, all of the patients do fasting plasma glucose (FPG), after eating 2 h blood sugar (PBG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS), after eating 2 h insulin (2 hINS), fasting C peptide (FCP), after eating 2 hC peptide (2 hCP), high-density lipoprotein (HDL), low density lipoprotein (LDL) examination.Results:Through the inspection analysis, duration, and 2 hINS FPG, FCP, 2 hCP, PBG, TG has obvious difference (P0.05), 62 cases of patients with T1DM appeared in 28 patients DPN, 24 cases of T2DM patients with diabetes in 7 cases appear DPN.Conclusion:The influence factors of DPN more, age, duration is a major risk factor for DPN, good blood glucose control, can effectively prevent the occurrence of DPN.

  17. Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women.

    Science.gov (United States)

    Sir-Petermann, T; López, G; Castillo, T; Calvillán, M; Rabenbauer, B; Wildt, L

    1998-01-01

    A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 Kg/m2) with hyperandrogenism (HA) and with normal glucose tolerance test were studied to evaluate the involvement of endogenous opioids in the pathophysiology of insulin secretion and insulin sensitivity in HA by administering naltrexone, an oral opioid receptor antagonist. Six patients received naltrexone orally (75 mg daily) and another six received placebo for 12 weeks (double-blind study). Before and after therapy a frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plasma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samples, before and after therapy. Treatment with naltrexone in hyperandrogenic patients resulted in a decrease in fasting insulin concentrations of 40% and C-peptide concentrations of 50% (p naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltrexone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or placebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administration. However, glucose effectiveness increased significantly with naltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucose (fasting and area under the curve) was not modified significantly after naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment with naltrexone or placebo. In conclusion, these results support the hypothesis of elevated opioid tonus and increased insulin secretion as a possible mechanism of hyperinsulinism in a group of hyperandrogenic women of ovarian origin. This alteration could act as an additional factor in the pathogenesis of insulin resistance found in an important proportion of these patients. PMID:9831304

  18. Roux-en-Y gastric bypass for Chinese type 2 diabetes mellitus patients with a BMI < 28 kg/m2: a multi-institutional study

    Institute of Scientific and Technical Information of China (English)

    Hui Liang; Wei Guan; Yanling Yang; Zhongqi Mao; Yijun Mei; Huan Liu; Yi Miao

    2015-01-01

    Roux-en-Y gastric bypass surgery (RYGB) has been demonstrated to be successful for treating type-Ⅱ diabetes mellitus (T2DM) patients with a body mass index (BMI) <30 kg/m2,but reports of RYGB for T2DM patients with a BMI <28 kg/m2 are lacking.T2DM patients with a BMI <28 kg/m2 were prospectively recruited to participate in this study in four hospitals.The endpoint was T2DM remission (defined by fasting blood glucose (FBG) level <110 mg/dL and hemoglobin (Hb)A1c level <6.0% at 12 months postoperatively).Predictors of remission were investigated by univariate and multivariate analyses.Eighty-six patients were assessed.Eighty-five patients underwent RYGB,with one conversion to open surgery.We compared the values of various variables before and after surgery.The mean BMI decreased from 24.68 ± 2.12 to 21.72 ± 2.43 kg/m2 (P<0.001).Fifty-eight (67.4%) patients were not treated by drugs or insulin after surgery,and 20 patients (23.3%) had complete remission of T2DM at 12 months after surgery with an acceptable number of complications.The mean HbA1c level in the remission group was significantly lower than that in the non-remission group.Patients with a higher weight,lower HbA1c level,higher C-peptide level,and higher FBG level were more likely to have T2DM remission in multivariate analyses.In conclusion,RYGB was effective and safe for treating T2DM patients with a BMI <28 kg/m2.Complete remission can be predicted by cases having a higher weight,lower HbA1c level,higher C-peptide level,and higher FBG level.

  19. Spontaneous hypoglycemia: diagnostic evaluation and management.

    Science.gov (United States)

    Kandaswamy, Leelavathy; Raghavan, Rajeev; Pappachan, Joseph M

    2016-07-01

    Spontaneous hypoglycemia is a puzzling clinical problem and an important reason for referral to endocrinologists. Several clinical conditions such as insulinomas, non-insulinoma pancreatogenous hypoglycemia syndrome, insulin autoimmune syndrome, postprandial hypoglycemia (reactive hypoglycemia), non-islet cell tumor hypoglycemia, primary adrenal insufficiency, hypopituitarism, and critical illness can be associated with spontaneous hypoglycemia. Rarely, in patients with mental health issues, factious hypoglycemia from extrinsic insulin use or ingestion of oral hypoglycemic agents can obfuscate the clinical picture for clinicians trying to identify an organic cause. In those presenting with Whipple's triad (symptoms ± signs of hypoglycemia, low plasma glucose, and resolution symptoms ± signs after hypoglycemia correction), a 72-h supervised fast test with measurement of plasma insulin, c-peptide, pro-insulin, and beta-hydroxybutyrate levels, coupled with plasma/urine sulphonylurea screen, forms the first step in diagnostic evaluation. A mixed meal test is preferable for those with predominantly postprandial symptoms. Additional non-invasive and/or invasive diagnostic evaluation is necessary if an organic hypoglycemic disorder is suspected. With the aid of a few brief clinical case scenarios, we discuss the diagnostic evaluation and management of spontaneous hypoglycemia through this comprehensive article. PMID:26951054

  20. Profound Hypoglycemia with Ecstasy Intoxication

    Directory of Open Access Journals (Sweden)

    Perliveh Carrera

    2015-01-01

    Full Text Available Background. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is a synthetic drug that is commonly abused for its stimulant and euphoric effects. Adverse MDMA effects include hyperthermia, psychomotor agitation, hemodynamic compromise, renal failure, hyponatremia, and coma. However, endogenous hyperinsulinemia with severe persistent hypoglycemia has not been reported with MDMA use. Case Report. We report the case of a 29-year-old woman who remained severely hypoglycemic requiring continuous intravenous infusion of high-dose dextrose solutions for more than 24 hours after MDMA intoxication. Serum insulin and C-peptide levels confirmed marked endogenous hyperinsulinemia as the cause of the severe hypoglycemia. Why Should an Emergency Physician Be Aware of This? Immediate and frequent monitoring of blood glucose should be instituted in patients presenting with MDMA ingestion particularly if found to be initially hypoglycemic. Early recognition can help prevent the deleterious effects of untreated hypoglycemia that can add to the morbidity from MDMA use. Clinicians need to be aware of this side effect of MDMA so they can carefully monitor and treat it, especially in patients presenting with altered mental status.

  1. The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth.

    LENUS (Irish Health Repository)

    Walsh, Jennifer M

    2013-05-01

    Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

  2. Targeting ligand-functionalized and redox-sensitive heparin-Pluronic nanogels for intracellular protein delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Dai Hai; Joung, Yoon Ki; Choi, Jong Hoon; Park, Ki Dong [Department of Molecular Science and Technology, Ajou University, 5 Wonchon, Yeoungtong, Suwon 443-749 (Korea, Republic of); Moon, Hyun Tae, E-mail: kdp@ajou.ac.kr [Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2011-10-15

    The heparin-Pluronic (HP) conjugate was coupled via redox-sensitive disulfide bond and contains a vinyl sulfone (VS) group with high reactivity to some functional groups such as thiol group. Heparin was conjugated with cystamine and the terminal hydroxyl groups of Pluronic were activated with the VS group, followed by coupling of VS groups of Pluronic with cystamine of heparin. The chemical structure, heparin content and VS group content of the resulting product were determined by {sup 1}H NMR, FT-IR, toluidine blue assay and Ellman's method. The HP conjugate formed a type of nanogel in an aqueous medium, showing a critical micelle concentration of approximately 129.35 mg L{sup -1}, a spherical shape and the mean diameter of 115.7 nm, which were measured by AFM and DLS. The release test demonstrated that HP nanogel was rapidly degraded when treated with glutathione. Cytotoxicity results showed a higher viability of drug-free HP nanogel than that of drug-loaded one. Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGDfC) peptide was efficiently conjugated to VS groups of HP nanogel and exhibited higher cellular uptake than unmodified nanogels. All results suggest a novel multi-functional nanocarrier delivery and effective release of proteins to the intracellular region in a redox-sensitive manner.

  3. [Development of microchips for the analysis of biomarkers in blood].

    Science.gov (United States)

    Kataoka, Masatoshi; Abe, Kaori; Hashimoto, Yoshiko; Yamamura, Shohei; Yatsushiro, Shouki

    2012-11-01

    Several types of microchips have been developed for application in clinical diagnosis. A microchip made of cyclic olefin copolymer with straight microchannels (300 microm width and 100 microm depth) was employed for sandwich ELISA for the determination of serum type I C-peptide (PICP), a biomarker of osteoporosis. This assay enabled us to determine PICP with accuracy and high sensitivity, reducing the time for the immunoassay to 1/6, and the consumption of samples and reagents to 1/50 compared with the conventional method. Furthermore, cell microarray chips with 20,944 microchambers (105 microm width and 50 microm depth), made of polystyrene, were employed for malaria diagnosis and the detection of carcinoma cells among the leukocytes. Around 100 erythrocytes or leukocytes were accommodated in each microchamber with the formation of a monolayer. For malaria diagnosis, it offered 10-100 times higher sensitivity in the detection of malaria infected erythrocytes than conventional light microscopy, and easy operation within 15 min. By double staining for epithelial cells on the cell microarray chip, one carcinoma cell could be detected among 1,800,000 leukocytes. These results indicate the potential of microchips for clinic diagnosis.

  4. A new relaxin-like gonad-stimulating peptide identified in the starfish Asterias amurensis.

    Science.gov (United States)

    Mita, Masatoshi; Daiya, Misaki; Haraguchi, Shogo; Tsutsui, Kazuyoshi; Nagahama, Yoshitaka

    2015-10-01

    Relaxin-like gonad-stimulating peptide (RGP) of starfish Asterina pectinifera was the first invertebrate gonadotropin to have its chemical structure identified. However, it is unclear whether gonadotropic hormones in other species starfish are relaxin-like peptides. Thus, this study tried to identify the molecular structure of gonadotropic hormone in Asterias amurensis. As a result, we identified A. amurensis gonadotropic hormone as the RGP (AamRGP). The DNA sequence encoding AamRGP consisted of 330 base pairs with an open reading frame encoding a peptide of 109 amino acids (aa), including a signal peptide (26 aa), B-chain (20 aa), C-peptide (38 aa) and A-chain (25 aa). Comparing with A. pectinifera RGP (ApeRGP), the amino acid identity levels between AmaRGP and ApeRGP were 58% for the A-chain and 73% for the B-chain. Furthermore, chemical synthetic AamRGP induced gamete spawning and oocyte maturation in ovarian fragments of A. amurensis. In contrast, the ovary of A. pectinifera failed to respond to the AamRGP. This suggested that AamRGP is a new relaxin-like peptide.

  5. A relaxin-like gonad-stimulating peptide from the starfish Aphelasterias japonica.

    Science.gov (United States)

    Mita, Masatoshi; Katayama, Hidekazu

    2016-04-01

    Relaxin-like gonad-stimulating peptide (RGP) in starfish is the first identified invertebrate gonadotropin responsible for final gamete maturation. In this study, a new ortholog RGP was identified from Aphelasterias japonica. The DNA sequence encoding A. japonica RGP (AjaRGP) consists of 342 base pairs with an open reading frame encoding a peptide of 113 amino acids (aa), including a signal peptide (26aa), B-chain (20aa), C-peptide (42aa), and A-chain (25aa). AjaRGP is a heterodimeric peptide with disulfide cross-linkages. Comparing with Asterias amurensis RGP (AamRGP) and Patiria (=Asterina) pectinifera RGP (PpeRGP), the amino acid identity levels of AjaRGP with respect to AamRGP and PpeRGP are 84% and 58% for the A-chain and 90% and 68% for the B-chain, respectively. This suggests that AjaRGP is closer to AmaRGP rather than PpeRGP. Although chemical synthetic AjaRGP can induce gamete spawning and oocyte maturation in ovarian fragments of A. japonica, the ovary of P. pectinifera fails to respond to AjaRGP. This suggests that AjaRGP acts species-specifically.

  6. Nephrilin peptide modulates a neuroimmune stress response in rodent models of burn trauma and sepsis

    Science.gov (United States)

    Mascarenhas, Desmond D; ElAyadi, Amina; Singh, Baljit K; Prasai, Anesh; Hegde, Sachin D; Herndon, David N; Finnerty, Celeste C

    2013-01-01

    Sepsis occurs three times more often in burns than in other types of trauma, suggesting an overlap or synergy between underlying immune mechanisms in burn trauma and sepsis. Nephrilin peptide, a designed inhibitor of mTORC2, has previously been shown to modulate a neuroimmune stress response in rodent models of xenobiotic and metabolic stress. Here we investigate the effect of nephrilin peptide administration in different rodent models of burn trauma and sepsis. In a rat scald burn model, daily subcutaneous bolus injection of 4 mg/kg nephrilin significantly reduced the elevation of kidney tissue substance P, S100A9 gene expression, PMN infiltration and plasma inflammatory markers in the acute phase, while suppressing plasma CCL2 and insulin C-peptide, kidney p66shc-S36 phosphorylation and PKC-beta and CGRP in dorsal root ganglia at 14 days (chronic phase). In the mouse cecal ligation and puncture model of sepsis, nephrilin fully protected mice from mortality between surgery and day 7, compared to 67% mortality in saline-treated animals, while significantly reducing elevated CCL2 in plasma. mTORC2 may modulate important neuroimmune responses in both burn trauma and sepsis. PMID:24273694

  7. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

    Science.gov (United States)

    Voruganti, V Saroja; Göring, Harald H H; Diego, Vincent P; Cai, Guowen; Mehta, Nitesh R; Haack, Karin; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2007-10-01

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

  8. A Modified Method of Insulin Producing Cells’ Generation from Bone Marrow-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Paweł Czubak

    2014-01-01

    Full Text Available Type 1 diabetes mellitus is a result of autoimmune destruction of pancreatic insulin producing β-cells and so far it can be cured only by insulin injection, by pancreas transplantation, or by pancreatic islet cells’ transplantation. The methods are, however, imperfect and have a lot of disadvantages. Therefore new solutions are needed. The best one would be the use of differentiated mesenchymal stem cells (MSCs. In the present study, we investigated the potential of the bone marrow-derived MSCs line for in vitro differentiation into insulin producing cells (IPSs. We applied an 18-day protocol to differentiate MSCs. Differentiating cells formed cell clusters some of which resembled pancreatic islet-like cells. Using dithizone we confirmed the presence of insulin in the cells. What is more, the expression of proinsulin C-peptide in differentiated IPCs was analyzed by flow cytometry. For the first time, we investigated the influence of growth factors’ concentration on IPCs differentiation efficiency. We have found that an increase in the concentration of growth factors up to 60 ng/mL of β-FGF/EGF and 30 ng/mL of activin A/β-cellulin increases the percentage of IPCs. Further increase of growth factors does not show any increase of the percentage of differentiated cells. Our findings suggest that the presented protocol can be adapted for differentiation of insulin producing cells from stem cells.

  9. A modified method of insulin producing cells' generation from bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Czubak, Paweł; Bojarska-Junak, Agnieszka; Tabarkiewicz, Jacek; Putowski, Lechosław

    2014-01-01

    Type 1 diabetes mellitus is a result of autoimmune destruction of pancreatic insulin producing β-cells and so far it can be cured only by insulin injection, by pancreas transplantation, or by pancreatic islet cells' transplantation. The methods are, however, imperfect and have a lot of disadvantages. Therefore new solutions are needed. The best one would be the use of differentiated mesenchymal stem cells (MSCs). In the present study, we investigated the potential of the bone marrow-derived MSCs line for in vitro differentiation into insulin producing cells (IPSs). We applied an 18-day protocol to differentiate MSCs. Differentiating cells formed cell clusters some of which resembled pancreatic islet-like cells. Using dithizone we confirmed the presence of insulin in the cells. What is more, the expression of proinsulin C-peptide in differentiated IPCs was analyzed by flow cytometry. For the first time, we investigated the influence of growth factors' concentration on IPCs differentiation efficiency. We have found that an increase in the concentration of growth factors up to 60 ng/mL of β-FGF/EGF and 30 ng/mL of activin A/β-cellulin increases the percentage of IPCs. Further increase of growth factors does not show any increase of the percentage of differentiated cells. Our findings suggest that the presented protocol can be adapted for differentiation of insulin producing cells from stem cells. PMID:25405207

  10. High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Johan F Paulsson

    Full Text Available AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes. RESULTS: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224 were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L were found in 11% (25/224. The IAPP increase did not correlate with C-peptide levels. CONCLUSIONS/INTERPRETATION: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.

  11. Type 2 diabetes in children: Clinical aspects and risk factors.

    Science.gov (United States)

    Rao, P V

    2015-04-01

    A strong link between obesity, insulin resistance, and metabolic syndrome has been reported with development of a new paradigm to type 2 diabetes mellitus (T2DM), with some evidence suggesting that beta-cell dysfunction is present before the onset of impaired glucose tolerance. Differentiating type 1 diabetes mellitus (T1DM) from T2DM is actually not very easy and there exists a number of overlapping characteristics. The autoantibody frequencies of seven antigens in T1DM patients may turn out to be actually having T2DM patients (pre-T2DM). T2DM patients generally have increased C-peptide levels (may be normal at time of diagnosis), usually no auto-antibodies, strong family history of diabetes, obese and show signs of insulin resistance (hypertension, acanthosis, PCOS). The American Academy of Paediatrics recommends lifestyle modifications ± metformin when blood glucose is 126-200 mg/dL and hemoglobin A1c (HbA1c) 200 mg/dL and HbA1c >8.5, with or without ketosis. Metformin is not recommended if the patient is ketotic, because this increases the risk of lactic acidosis. Metformin is currently the only oral hypoglycemic that has been approved for use in children. Knowing these subtle differences in mechanism, and knowing how to test patients for which mechanism (s) are causing their diabetes mellitus, may help us eventually tailor treatment programs on an individual basis.

  12. Type 2 diabetes in children: Clinical aspects and risk factors

    Directory of Open Access Journals (Sweden)

    P V Rao

    2015-01-01

    Full Text Available A strong link between obesity, insulin resistance, and metabolic syndrome has been reported with development of a new paradigm to type 2 diabetes mellitus (T2DM, with some evidence suggesting that beta-cell dysfunction is present before the onset of impaired glucose tolerance. Differentiating type 1 diabetes mellitus (T1DM from T2DM is actually not very easy and there exists a number of overlapping characteristics. The autoantibody frequencies of seven antigens in T1DM patients may turn out to be actually having T2DM patients (pre-T2DM. T2DM patients generally have increased C-peptide levels (may be normal at time of diagnosis, usually no auto-antibodies, strong family history of diabetes, obese and show signs of insulin resistance (hypertension, acanthosis, PCOS. The American Academy of Paediatrics recommends lifestyle modifications ± metformin when blood glucose is 126-200 mg/dL and hemoglobin A1c (HbA1c 200 mg/dL and HbA1c >8.5, with or without ketosis. Metformin is not recommended if the patient is ketotic, because this increases the risk of lactic acidosis. Metformin is currently the only oral hypoglycemic that has been approved for use in children. Knowing these subtle differences in mechanism, and knowing how to test patients for which mechanism (s are causing their diabetes mellitus, may help us eventually tailor treatment programs on an individual basis.

  13. Increased metabolic rate in obese women after ingestion of potassium, magnesium- and phosphate-enriched orange juice or injection of ephedrine.

    Science.gov (United States)

    Jaedig, S; Henningsen, N C

    1991-06-01

    Thirty-six obese, pre-menopausal women were studied after an overnight fast and randomized to four different regimens of metabolic stimuli: group I (n = 12), 100 ml orange juice with dissolved K- and Mg-phosphates (K, 40 mmol; Mg, 17.5 mmol; HPO4, 35 mmol); group II (n = 8), 100 ml of water with electrolytes as in group I; group III (n = 8), 100 ml of orange juice; group IV (n = 8), injection of ephedrine intravenously, 0.25 mg/kg body weight. The women in groups I, II and III were further stimulated with ephedrine as in group IV and new measurements made. Thirty minutes after the first stimulus VO2, VCO2 and energy expenditure (EE) rose significantly (13.1-16.5 per cent) in groups I and IV only. In groups I and III the blood concentrations of glucose, insulin, and C-peptide rose significantly. After the second stimulus (ephedrine i.v.) no further increase in VO2, VCO2 and EE occurred in group I, but the increases from basal values became significant in group III. In all women at baseline, whole-body potassium was significantly correlated to VO2. Serum-magnesium was negatively correlated to A/I weight (actual/ideal weight). We conclude that the addition of K- and Mg-phosphates to glucose increases the postprandial thermogenesis in obese patients.

  14. PREVALENCE OF TESTOSTERONE DEFICIENCY IN PATIENTS OF DIABETES MELLITUS LESS THAN 40 YEARS OF AGE

    Directory of Open Access Journals (Sweden)

    Praveen K

    2016-01-01

    Full Text Available BACKGROUND Diabetes mellitus is common endocrine disorder which involves multiple organs and leads to significant morbidity and mortality due to accompanying complications. Erectile dysfunction, reduced libido, orgasmic dysfunction, and retrograde ejaculation are established complications found with variable prevalence in men with diabetes. METHODOLOGY In the present study, total 90 male patients of diabetes mellitus of age below 40 years were taken from medical outpatient department and indoor patients of medical wards of a tertiary care teaching hospital of South Delhi. They were evaluated for complains regarding sexual dysfunction. Hormonal assays of serum free testosterone, LH, FSH, C-peptide, HbA1c and lipid profile were carried out in all patients. RESULT Present study shows that testosterone deficiency is quite common in young diabetic patients. Low serum free testosterone was more common in type 2 diabetes as compared to type 1 diabetes (38.46% Vs 29.41%. BMI has significant effect on serum free testosterone levels. Patients with higher BMI had negative correlation to free testosterone although testosterone deficiency was also seen in few lean patients. High serum triglyceride and low serum HDL were seen more frequently in patients with low free testosterone. CONCLUSION This study reveals that hypogonadism is not a rarity even at initial stages of diabetes. This study, although small, highlights importance of assessment of young diabetic patients for sexual dysfunction and hypogonadism.

  15. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S. (Karolinska Hospital, Stockholm (Sweden))

    1990-11-01

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with (2-3H)glucose and HGP with (6-3H)glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). (2-3H)- minus (6-3H)glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP.

  16. Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Calanna, Salvatore; Sparre-Ulrich, Alexander H;

    2015-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) is glucagonotropic, and glucagon-like peptide-1 (GLP-1) is glucagonostatic. We studied the effects of GIP and GLP-1 on glucagon responses to insulin-induced hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Ten male subjects with T1DM...... days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 [GIP] vs. 232 ± 40 [GLP-1] vs. 212 ± 56 [saline] mg ⋅ kg(-1), P < 0.05). Levels of insulin, cortisol, growth hormone, and noradrenaline, as well as hypoglycemic symptoms and cognitive function, were...... (C-peptide negative, age [mean ± SEM] 26 ± 1 years, BMI 24 ± 0.5 kg/m(2), HbA1c 7.3 ± 0.2%) were studied in a randomized, double-blinded, crossover study, with 2-h intravenous administration of saline, GIP, or GLP-1. The first hour, plasma glucose was lowered by insulin infusion, and the second hour...

  17. Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent.

    Science.gov (United States)

    Kuo, Sheng-Fong; Chuang, Wen-Yu; Ng, Sohching; Chen, Chih-Hung; Chang, Chen-Nen; Chou, Chi-Hsiang; Weng, Wei-Chieh; Yeh, Chih-Hua; Lin, Jen-Der

    2013-01-01

    Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.

  18. Establishment of LC-MS methods for the analysis of palmitoylated surfactant proteins.

    Science.gov (United States)

    Harayama, Takeshi; Shindou, Hideo; Kita, Yoshihiro; Otsubo, Eiji; Ikeda, Kazushige; Chida, Shoichi; Weaver, Timothy E; Shimizu, Takao

    2015-07-01

    The surfactant proteins (SPs), SP-B and SP-C, are important components of pulmonary surfactant involved in the reduction of alveolar surface tension. Quantification of SP-B and SP-C in surfactant drugs is informative for their quality control and the evaluation of their biological activity. Western blot analysis enabled the quantification of SP-B, but not SP-C, in surfactant drugs. Here, we report a new procedure involving chemical treatments and LC-MS to analyze SP-C peptides. The procedure enabled qualitative analysis of SP-C from different species with discrimination of the palmitoylation status and the artificial modifications that occur during handling and/or storage. In addition, the method can be used to estimate the total amount of SP-C in pulmonary surfactant drugs. The strategy described here might serve as a prototype to establish analytical methods for peptides that are extremely hydrophobic and behave like lipids. The new method provides an easy measurement of SP-C from various biological samples, which will help the characterization of various experimental animal models and the quality control of surfactant drugs, as well as diagnostics of human samples. PMID:26022805

  19. Glucose metabolism alterations in patients with bipolar disorder.

    Science.gov (United States)

    Rosso, Gianluca; Cattaneo, Annamaria; Zanardini, Roberta; Gennarelli, Massimo; Maina, Giuseppe; Bocchio-Chiavetto, Luisella

    2015-09-15

    Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder. PMID:26120808

  20. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells

    Science.gov (United States)

    Zalzman, Michal; Gupta, Sanjeev; Giri, Ranjit K.; Berkovich, Irina; Sappal, Baljit S.; Karnieli, Ohad; Zern, Mark A.; Fleischer, Norman; Efrat, Shimon

    2003-06-01

    Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.

  1. Insulin Independence after Fetal Liver-Derived Cell Suspension Al¬lotransplantation in Patients with Type 1 Diabetes: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Maryam GHODSI

    2015-10-01

    Full Text Available Background: Cell-based treatments are currently being actively received great attention among scientists and clinicians for a variety of diseases as well as diabetes .The aim of this study was to investigate the effect of allotransplantation of fetal liver-derived cell suspension in patients with type 1 diabetes.Methods: Patients with type 1 diabetes (n=16 aged 6-30 years-old were included in the study. Fetal liver-derived cell suspension was transplanted by the means of intravenous injection patient.Results: In most of patient, blood glucose levels gradually decreased within the first day of infusion. Insulin independence occurred in 3 patients out of the 16 (18.7% for 4 to 24 months. They showed increasing levels of serum c-peptide along with decreasing of levels of HbA1c level. In other patients, no significant changes in parameters of diabetes control were observed. Conclusion: Findings of this study indicated that transplantation of fetal stem cells could, although not permanently, be an effective therapeutic intervention in patients with type 1 diabetes. To demonstrate effectiveness of stem-cell therapy for treatment of diabetes, more clinical trials with stricter inclusion criteria, modified protocols, and larger number of patients and are necessary as well as long periods of follow up. Keywords: Stem cell, Type 1 diabetes, Allotransplantation, Fetal Liver-Derived Cell Suspension, Cell Therapy

  2. Production of islet-like insulin-producing cell clusters in vitro from adipose-derived stem cells

    Directory of Open Access Journals (Sweden)

    Loan Thi-Tung Dang

    2015-01-01

    Full Text Available Diabetes mellitus is a high incidence disease that has increased rapidly in recent years. Many new therapies are being studied and developed in order to find an effective treatment. An ideal candidate is stem cell therapy. In this study, we investigated the differentiation of adipose derived stem cells (ADSCs into pseudo-islets in defined medium in vitro, to produce large quantities of insulin-producing cells (IPCs for transplantation. ADSCs isolated from adipose tissue were induced to differentiate into islet-like insulin-producing cell clusters in vitro by inducing medium DMEM/F12 containing nicotinamide, N2, B27, bFGF, and insulin-transferrin-selenite (ITS. Differentiated cells were analyzed for properties of IPCs, including storage of Zn2+ by dithizone staining, insulin production by ELISA and immunochemistry, and beta cell-related gene expression by reverse transcriptase PCR. The results showed that after 2 weeks of differentiation, the ADSCs aggregated into cell clusters, and after 4 weeks they formed islets, 50 and ndash;400 micrometers in diameter. These islet cells exhibited characteristics of pancreatic beta cells as they were positive for dithizone staining, expressed insulin in vitro and C-peptide in the cytoplasm, and expressed pancreatic beta cell-specific genes, including Pdx-1, NeuroD, and Ngn3. These results demonstrate that ADSCs can be used to produce a large number of functional islets for research as well as application. [Biomed Res Ther 2015; 2(1.000: 184-192

  3. Differentiation of mouse embryonic stem cells into endoderm without embryoid body formation.

    Directory of Open Access Journals (Sweden)

    Peter T W Kim

    Full Text Available Pluripotent embryonic stem cells hold a great promise as an unlimited source of tissue for treatment of chronic diseases such as Type 1 diabetes. Herein, we describe a protocol using all-trans-retinoic acid, basic fibroblast growth factor and dibutyryl cAMP (DBcAMP in the absence of embryoid body formation, for differentiation of murine embryonic stem cells into definitive endoderm that may serve as pancreatic precursors. The produced cells were analyzed by quantitative PCR, immunohistochemistry and static insulin release assay for markers of trilaminar embryo, and pancreas. Differentiated cells displayed increased Sox17 and Foxa2 expression consistent with definitive endoderm production. There was minimal production of Sox7, an extraembryonic endoderm marker, and Oct4, a marker of pluripotency. There was minimal mesoderm or neuroectoderm formation based on expression levels of the markers brachyury and Sox1, respectively. Various assays revealed that the cell clusters generated by this protocol express markers of the pancreatic lineage including insulin I, insulin II, C-peptide, PDX-1, carboxypeptidase E, pan-cytokeratin, amylase, glucagon, PAX6, Ngn3 and Nkx6.1. This protocol using all-trans-retinoic acid, DBcAMP, in the absence of embryoid bodies, generated cells that have features of definitive endoderm that may serve as pancreatic endocrine precursors.

  4. Multiple intravenous infusions of bone marrow mesenchymal stem cells reverse hyperglycemia in experimental type 2 diabetes rats.

    Science.gov (United States)

    Hao, Haojie; Liu, Jiejie; Shen, Jing; Zhao, Yali; Liu, Huilin; Hou, Qian; Tong, Chuan; Ti, Dongdong; Dong, Liang; Cheng, Yu; Mu, Yiming; Liu, Jianping; Fu, Xiaobing; Han, Weidong

    2013-07-01

    The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Single-dose mesenchymal stem cell (MSC) infusion ameliorates hyperglycemia but fails to restore normoglycemia in diabetic animals. We therefore hypothesized that multiple intravenous MSC infusions may reverse hyperglycemia in type 2 diabetes (T2D) rats. We administered serial allogenous bone-marrow derived MSC infusions (1 × 10(6)cells/infusion) via the tail vein once every 2 weeks to T2D rats, induced by high-fat diet and streptozocin (STZ) administration. Hyperglycemia decreased only transiently after a single infusion in early-phase (1 week) T2D rats, but approximated normal levels after at least three-time infusions. This normal blood level was maintained for at least 9 weeks. Serum concentrations of both insulin and C-peptide were dramatically increased after serial MSC infusions. Oral glucose tolerance tests revealed that glucose metabolism was significantly ameliorated. Immunofluorescence analysis of insulin/glucagon staining revealed the restoration of islet structure and number after multiple MSC treatments. When multiple-MSC treatment was initiated in late-phase (5 week) T2D rats, the results were slightly different. The results of this study suggested that a multiple-MSC infusion strategy offers a viable clinical option for T2D patients.

  5. Autoimmune diabetes is suppressed by treatment with recombinant human tissue Kallikrein-1.

    Science.gov (United States)

    Maneva-Radicheva, Lilia; Amatya, Christina; Parker, Camille; Ellefson, Jacob; Radichev, Ilian; Raghavan, Arvind; Charles, Matthew L; Williams, Mark S; Robbins, Mark S; Savinov, Alexei Y

    2014-01-01

    The kallikrein-kinin system (KKS) comprises a cascade of proteolytic enzymes and biogenic peptides that regulate several physiological processes. Over-expression of tissue kallikrein-1 and modulation of the KKS shows beneficial effects on insulin sensitivity and other parameters relevant to type 2 diabetes mellitus. However, much less is known about the role of kallikreins, in particular tissue kallikrein-1, in type 1 diabetes mellitus (T1D). We report that chronic administration of recombinant human tissue kallikrein-1 protein (DM199) to non-obese diabetic mice delayed the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a dose- and treatment frequency-dependent manner. Suppression of the autoimmune reaction against pancreatic beta cells was evidenced by a reduction in the relative numbers of infiltrating cytotoxic lymphocytes and an increase in the relative numbers of regulatory T cells in the pancreas and pancreatic lymph nodes. These effects may be due in part to a DM199 treatment-dependent increase in active TGF-beta1. Treatment with DM199 also resulted in elevated C-peptide levels, elevated glucagon like peptide-1 levels and a reduction in dipeptidyl peptidase-4 activity. Overall, the data suggest that DM199 may have a beneficial effect on T1D by attenuating the autoimmune reaction and improving beta cell health. PMID:25259810

  6. Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes.

    Directory of Open Access Journals (Sweden)

    Carlos C Barros

    Full Text Available The Kallikrein-Kinin System (KKS has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM, we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO. Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

  7. Autoimmune diabetes is suppressed by treatment with recombinant human tissue Kallikrein-1.

    Directory of Open Access Journals (Sweden)

    Lilia Maneva-Radicheva

    Full Text Available The kallikrein-kinin system (KKS comprises a cascade of proteolytic enzymes and biogenic peptides that regulate several physiological processes. Over-expression of tissue kallikrein-1 and modulation of the KKS shows beneficial effects on insulin sensitivity and other parameters relevant to type 2 diabetes mellitus. However, much less is known about the role of kallikreins, in particular tissue kallikrein-1, in type 1 diabetes mellitus (T1D. We report that chronic administration of recombinant human tissue kallikrein-1 protein (DM199 to non-obese diabetic mice delayed the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a dose- and treatment frequency-dependent manner. Suppression of the autoimmune reaction against pancreatic beta cells was evidenced by a reduction in the relative numbers of infiltrating cytotoxic lymphocytes and an increase in the relative numbers of regulatory T cells in the pancreas and pancreatic lymph nodes. These effects may be due in part to a DM199 treatment-dependent increase in active TGF-beta1. Treatment with DM199 also resulted in elevated C-peptide levels, elevated glucagon like peptide-1 levels and a reduction in dipeptidyl peptidase-4 activity. Overall, the data suggest that DM199 may have a beneficial effect on T1D by attenuating the autoimmune reaction and improving beta cell health.

  8. Sequences of stilboflavin C: towards the peptaibiome of the filamentous fungus Stilbella (= Trichoderma) flavipes.

    Science.gov (United States)

    Degenkolb, Thomas; Götze, Lutz; von Döhren, Hans; Vilcinskas, Andreas; Brückner, Hans

    2016-08-01

    Filamentous fungi of the genus Stilbella are recognized as an abundant source of naturally occurring α-aminoisobutyric acid-containing peptides. The culture broth of Stilbella (Trichoderma) flavipes CBS 146.81 yielded a mixture of peptides named stilboflavins (SF), and these were isolated and separated by preparative TLC into groups named SF-A, SF-B, and SF-C. Although all three of these groups resolved as single spots on thin-layer chromatograms, HPLC analysis revealed that each of the groups represents very microheterogeneous mixtures of closely related peptides. Here, we report on the sequence analysis of SF-C peptides, formerly isolated by preparative TLC. HPLC coupled to QqTOF-ESI-HRMS provided the sequences of 10 16-residue peptides and five 19-residue peptides, all of which were N-terminally acetylated. In contrast to the previously described SF-A and SF-B peptaibols, SF-C peptaibols contain Ser-Alaol or Ser-Leuol, which are rarely found as C-termini, and repetitive Leu-Aib-Gly sequences, which have not been detected in peptaibols before. Taking the previously determined sequences of SF-A and SF-B into account, the entirety of peptides produced by S. flavipes (the 'peptaibiome') approaches or exceeds 100 non-ribosomally biosynthesized peptaibiotics. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27443977

  9. Pancreatic insulinomas:laparoscopic management

    Institute of Scientific and Technical Information of China (English)

    Pantelis; T; Antonakis; Hutan; Ashrafian; Alberto; Martinez-Isla

    2015-01-01

    Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign,solitary,and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple’s triad,along with corroborating measurements of blood glucose,insulin,proinsulin,C-peptide,β-hydroxybutyrate,and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this,careful preoperative planning is required,with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound,which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings,but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit,laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore,this approach confers equivalent safety and efficacy rates to open resection,while improving cosmesis and reducing hospital stay. As such,laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.

  10. Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion

    International Nuclear Information System (INIS)

    We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-MΦ). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-MΦ (CB f-MΦ) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-MΦ (TCB f-MΦ) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1, Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolyssacharide (LPS) and 25 mM glucose, the TCB f-MΦ differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-MΦ and may lead to develop new therapeutic strategy for treating dominant disease

  11. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

    Directory of Open Access Journals (Sweden)

    Anoopa A. Koshy MD

    2013-01-01

    Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

  12. Prehepatic secretion and disposal of insulin in obese adolescents as estimated by three-hour, eight-sample oral glucose tolerance tests.

    Science.gov (United States)

    Vogt, Josef A; Domzig, Christian; Wabitsch, Martin; Denzer, Christian

    2016-07-01

    The body compensates for early-stage insulin resistance by increasing insulin secretion. A reliable and easy-to-use mathematical assessment of insulin secretion and disposal could be a valuable tool for identifying patients at risk for the development of type 2 diabetes. Because the pathophysiology of insulin resistance is incompletely understood, assessing insulin metabolism with minimal assumptions regarding its metabolic regulation is a major challenge. To assess insulin secretion and indexes of insulin disposal, our marginalized and regularized absorption approach (MRA) was applied to a sparse sampling oral glucose tolerance test (OGTT) protocol measuring the insulin and C-peptide concentrations. Identifiability and potential bias of metabolic parameters were estimated from published data with dense sampling. The MRA was applied to OGTT data from 135 obese adolescents to demonstrate its clinical applicability. Individual prehepatic basal and dynamic insulin secretion and clearance levels were determined with a precision and accuracy greater than 10% of the nominal value. The intersubject variability in these parameters was approximately four times higher than the intrasubject variability, and there was a strong negative correlation between prehepatic secretion and plasma clearance of insulin. MRA-based analysis provides reliable estimates of insulin secretion and clearance, thereby enabling detailed glucose homeostasis characterization based on restricted datasets that are obtainable during routine patient care. PMID:27143555

  13. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy

    Science.gov (United States)

    Sarang, Shabari; Viswanathan, Chandra

    2016-01-01

    Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes. PMID:27426087

  14. 谷氨酸脱羧酶抗体在2型糖尿病患者中的检出率及分布特征%Analysis of the Detection Rate and Distrubution Feature of Glutamic Acid Decarboxylase Antibodies in Patients with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    张利方; 刘莹; 石莉萍; 汪薇

    2013-01-01

    Objective: To explore the change of detection rate and distribution feature of glutamic acid decarboxylase antibody (GAD-Ab) in patients with type 2 diabetes mellitus (T2DM). Method: To detect the positive rate of GAD-Ab using EL1SA method in 1970 patients with T2DM and its distribution in different sex, age, course of disease and body mass index (BM1). Fasting, postprandial insulin 2H (FINS, 2hLNS) and fasting, postprandial 2h C peptide (FCP, 2hCP) level were detected by electro-chemiluminescence in GAD-Ab positive and negative patients and compared with the healthy people. Results: 126 cases were GAD-Ab positive among the 1970 patients with T2DM and the total positive rate was 6. 39%. GAD-Ab was mainly distributed in patients during the 30 ~49 years old (P0.05).GAD-Ab阳性组T2DM FINS、2hINS、FCP和2hCP均低于GAD-Ab阴性组和健康对照组(P<0.05).结论:GAD-Ab检测有助于临床对T2DM患者胰岛素功能变化进行评价.

  15. IMMUNOLOGICAL AND METABOLIC FACTORS INTERACTION IN THE DEVELOPMENT AND PROGRESSION OF MICROVASCULAR COMPLICATIONS IN LATENT AUTOIMMUNE DIABETES OF ADULTS (LADA

    Directory of Open Access Journals (Sweden)

    T. V. Saprina

    2014-01-01

    Full Text Available Some researchers found that the development of microvascular complications (nephropathy, retinopathy with latent autoimmune diabetes adults (LADA occurs much earlier than in type 1 diabetes mellitus. The research devoted to the study of the spectrum and the time of development of microangiopathy in patients with latent autoimmune diabetes of adults, compared to patients with type 1 and 2 diabetes mellitus. Also studied immunological factors (cytokine secretion of mononuclear leukocytes as one of the possible mechanisms of diabetic angiopathy progression. It has been shown that in LADA, as in patients with type 2 diabetes mellitus, the development of microvascular complications (nephropathy, retinopathy occurs much earlier than in type 1 diabetes mellitus (after a 4-year course of the disease due to a sharp decline in the serum concentration of C peptide. Thus in patients with LADA, having microvascular complications in the supernatants of cell cultures of mononuclear leukocytes determined a significant increase in the concentrations of cytokines IL-2, IL-4, TNFα.

  16. Peptide isolated from Cry1Ab16 toxin present in Bacillus thuringiensis: Synthesis and morphology data for layer-by-layer films studied by atomic force microscopy.

    Science.gov (United States)

    Plácido, Alexandra; de Oliveira Farias, Emanuel Airton; Marani, Mariela M; Gomes Vasconcelos, Andreanne; Leite, José R S A; Delerue-Matos, Cristina

    2016-09-01

    The peptide PcL342-354C was obtained from the Cry1Ab16 toxin present in Bacillus thuringiensis ("Computational Modeling Deduced Three Dimensional Structure of Cry1Ab16 Toxin from B. thuringiensis AC11" (Kashyap, 2012) [1]). In this data article, we report the synthesis and characterization of the PcL342-354C peptide by MALDI-TOF/TOF mass spectrometry. In addition, the preparation of layer-by-layer films is shown based on interspersion of this peptide with both polyethylenimine (PEI) and poly(sodium 4-styrenesulfonate) (PSS), self-assembled on ITO (indium tin oxide) electrodes. The morphology of the ITO/PEI/PSS/PcL342-354C film was analyzed using atomic force microscopy (AFM). We also evaluated the effect of the number of bilayers in ITO/PEI/(PSS/PcL342-354C) n on the morphology of the film using AFM amplitude images. Further details about this study were published elsewhere, "Layer-by-layer films containing peptides of the Cry1Ab16 toxin from B. thuringiensis for potential biotechnological applications," (Plácido et al., 2016) [2]. PMID:27294178

  17. Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats.

    Science.gov (United States)

    El-Seweidy, Mohamed M; Sadik, Nermin A H; Shaker, Olfat G

    2011-02-01

    This study examined the downstream signaling whereby hyperglycemia may lead to myocardial fibrosis and apoptosis in the left ventricle of diabetic rats. The effects of sulfurous mineral water or sodium hydrosulfide (NaHS) as possible modulators were also examined. Sulfurous mineral water (as drinking water) and NaHS (14μmol/kg/day, IP) were administered for 7 week to rats with streptozotocin (STZ)-induced diabetes. Hyperglycemia, overproduction of glycated hemoglobin (HbA1C) and serum decline in insulin, C-peptide and insulin like growth factor-I (IGF-I) were observed in diabetic rats. Up-regulation of gene expressions of nuclear factor (NF-κB), profibrogenic growth factor such as transforming growth factor-β1 (TGF-β1), matrix metalloproteniase-2 (MMP-2), procollagen-1 and Fas ligand (Fas-L) were observed in the left ventricle of diabetic rats. A linear positive correlation between TGF-β1 and MMP-2 was also detected in diabetic group. An increase in hydroxyproline level and a disturbance in oxidative balance were detected in heart of diabetic rats. Sulfurous mineral water and NaHS treatment possibly, by improving cardiac GSH level, counteracted the enhanced expression of NF-κB, the profibrogenic and apoptotic parameters. Histopathological examination was in accordance with the biochemical and molecular findings of this study. We suggest a novel therapeutic approach of sulfurous mineral water and exogenous supplementation of H(2)S in diabetic cardiomyopathy.

  18. A pilot study showing associations between frequency of CD4(+) memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes.

    Science.gov (United States)

    Moya, Rosita; Robertson, Hannah Kathryn; Payne, Dawson; Narsale, Aditi; Koziol, Jim; Davies, Joanna Davida

    2016-05-01

    In some patients with type 1 diabetes the dose of insulin required to achieve euglycemia is substantially reduced soon after diagnosis. This partial remission is associated with β-cell function and good glucose control. The purpose of this study was to assess whether frequencies of CD4(+) T cell subsets in children newly diagnosed with type 1 diabetes are associated with length of partial remission. We found that the frequency of CD4(+) memory cells, activated Treg cells and CD25(+) cells that express a high density of the IL-7 receptor, CD127 (CD127(hi)) are strongly associated with length of partial remission. Prediction of length of remission via Cox regression is significantly enhanced when CD25(+) CD127(hi) cell frequency is combined with either Insulin Dependent Adjusted A1c (IDAA1c), or glycosylated hemoglobin (HbA1c), or C-peptide levels at diagnosis. CD25(+) CD127(hi) cells do not express Foxp3, LAG-3 and CD49b, indicating that they are neither Treg nor Tr1 cells. PMID:27114212

  19. Recurrent Hypoglycemia in a Patient with Hodgkin’s Lymphoma: A Case Report with Review of Literature

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    Rawal Gautam

    2016-09-01

    Full Text Available A rare complication associated with the Hodgkin’s lymphoma is the occurrence of persistent or recurrent hypoglycemia. Although few cases have been reported in the literature, describing its pathophysiology to be multifactorial, it is difficult to determine the exact cause. We present the case of a 26 year old patient diagnosed with Hodgkin’s lymphoma who developed recurrent episodes of hypoglycemia and also discuss the various causes for its pathogenesis. In this case the serum insulin and C-peptide levels were found to be low, suggesting the presence of insulin like growth factors (IGF secreted by the cancer cells. Also, we performed a18F-2-fluoro-2-deoxy-d-glucose positron emission tomography that showed a massive tumor load. The published reports in literature have similary suggested the presence of IGF or auto-antibodies secreted by the tumor cells and also the Warburg effect in patients with high tumor load. Further research is required to clearly diagnose and define the exact etiopathogenesis of the hypoglycemia occurring in a patient with Hodgkin’s lymphoma.

  20. Response of Chick B Islets to Insulin Secretagogues is Comparable to those of Human Islet Equivalents

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    Bhawna Chandravanshi

    2015-05-01

    Full Text Available Context The B islets isolated from 3-5 day old chick respond well to glucose challenge in a similar fashion to those isolated from mouse pancreas. Objective To compare insulin secretory response of chick B islets with that of human Islet Equivalents (hIEqs generated from stem cells. Methods Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs were differentiated into hIEqs employing three step sequential serum free protocols. Results Immunofluorescence staining demonstrated Insulin, C peptide and Glut 2 positivity of both these islets. Static insulin stimulation of these islets in response to glucose, metformin and Gama Amino Butyric Acid (GABA resulted in increased insulin secretion as compared to basal glucose stimulation. Our results demonstrate that insulin secretory response of Chick B islets to Metformin and GABA is comparable to those of hIEqs. Moreover, both chick and hIEqs could be successfully cryopreserved and revived in a commercially available cryomix - Cryostore 5, indicating resemblance in their behaviour at sub-zero temperatures. Inference Present study advocates Chick islets as an alternative source for diabetes research and islet banking.

  1. 8th quality control survey for radioisotope in vitro tests in Japan, 1986

    Energy Technology Data Exchange (ETDEWEB)

    1987-10-01

    This paper presents results of the 8th quality control survey, carried out in 480 facilities throughout Japan, for radioimmunoassay of the following 32 items: adrenocorticotropic hormone, ..cap alpha..-fetoprotein, aldosterone, ..beta../sub 2/-microglobulin, carbohydrate antigen 19 - 9, carcinoembryonic antigen, cortisol, C-peptide, digoxin, elastase 1, estradiol, ferritin, free triiodothyronine, free thyroxin, follicle stimulating hormone, gastrin, growth hormone, glucagon, immunoglobulin E, insulin, luteinizing hormone, prostatic acid phosphatase, progesterone, prolactin, parathyroid hormone, squamous cell carcinoma associated antigen, triiodothyronine, thyroxine, triiodothyronine uptake, thyroxin binding globulin, testosterone, thyroglobulin, tissue polypeptide antigen, and thyroid stimulaing hormone. Overall, 'between-assay' variation was in good agreement with 'within-kit' variation, suggesting the equal technical skills of the kit users among the facilities. A great discrepancy observed in the present assay results was, therefore, considered due to 'between-kit' variation. An international criteria for titers and the development of kits having antibodies with small cross reactivity are emphasized with the aim of improving differences in kits. (Namekawa, K.).

  2. The 13th quality control survey for radioisotopes in vitro tests in Japan, 1991

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-01

    This paper presents the results of the 13th quality control nationwide survey. Of 568 hospitals performing RI in vitro tests as of December 1991, 280 (49.3%) participated in this survey. The following 37 items were examined: ACTH, 17[alpha]-hydroxyprogesterone, [alpha]-fetoprotein, aldosterone, [beta]2-microglobulin, CA 125, CA 15-3, CA 19-9, calcitonin, CEA, cortisol, C-peptide, digoxin, esteradiol, ferritin, free triiodothyronine (T[sub 3]), free thyroxine (T[sub 4]), FSH, gastrin, GH, glucagon, IgE, insulin, LH, PAP, progesterone, prolactin, PTH, somatomedin C, T[sub 3], T[sub 4], T[sub 3] uptake, TBG, testosterone, thyroglobulin, tissue polypeptide antigen, and TSH. Reliability and safety of measurement values were evaluated based on protein components of serum samples, spontaneous reliability test, time-dependent reliability test, repeated freezing-dissolution test, and serial change test after freezing. 'Within kit variation' between facilities was great especially for ACTH, CA 15-3, CA 19-9, free T[sub 4], calcitonin, gastrin, and testosterone, and was favorable for [beta][sub 2]-microglobulin, CA 125, digoxin, cortisol, IgE, T[sub 3], T[sub 4], T[sub 3] uptake, and TBG. It was noted that there was a great difference in measurement values of free T[sub 3] and free-T[sub 4] between RIA kits and non-isotopic kits. (N.K.).

  3. Severe suicidal digoxin and propranolol toxicity with insulin overdose

    Directory of Open Access Journals (Sweden)

    Ashish Garg

    2014-01-01

    Full Text Available We present a case of a 32-year-old male doctor, with type I diabetes mellitus on daily insulin therapy, who allegedly consumed large doses of digoxin and propranolol along with simultaneous administration of large dose of insulin with suicidal intent. Initial investigations revealed serum digoxin levels of 7.5 ng/ml, serum insulin 500 μIU/ml, and serum C-peptide 0.43 ng/ml. He was managed with charcoal-based hemoperfusion for digoxin overdose along with injection glucagon for propranolol overdose. His blood sugar levels were maintained with continuous infusion of 20% dextrose till the patient was allowed to take oral diet. Significant clinical improvement was noticed with this therapy which was evident by progressively declining serum digoxin levels, normalization of pulse rate, and adequate blood glucose levels. Finally, with a good hemodynamic profile and a serum digoxin level well within normal limits, he was discharged following consultation with a psychiatrist.

  4. Serum TNF-Alpha Level Predicts Nonproliferative Diabetic Retinopathy in Children

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    Katarzyna Zorena

    2007-01-01

    Full Text Available The aim of this study was identification of the immunologic markers of the damage to the eye apparatus at early stages of diabetes mellitus (DM type 1 children. One hundred and eleven children with DM type 1 were divided into two groups: those with nonproliferative diabetic retinopathy (NPDR and without retinopathy. All the children had their daily urine albumin excretion, HbA1c, C-peptide measured, 24-hour blood pressure monitoring, and ophthalmologic examination. Levels of TNF-α, IL-6, and IL-12 in serum were measured by ELISA tests (Quantikine High Sensitivity Human by R&D Systems, Minneapolis, Minn, USA. The NPDR children demonstrated a significantly longer duration of the disease in addition to higher HbA1c, albumin excretion rate, C-reactive protein, systolic blood pressure, as well as TNF-α and IL-6 levels than those without retinopathy. The logistic regression revealed that the risk of NPDR was strongly dependent on TNF-α [(OR 4.01; 95%CI 2.01–7.96]. TNF-α appears to be the most significant predictor among the analyzed parameters of damage to the eye apparatus. The early introduction of the TNF-α antagonists to the treatment of young patients with DM type 1 who show high serum activity of the TNF-α may prevent them from development of diabetic retinopathy.

  5. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    Science.gov (United States)

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  6. Personalized medicine in diabetes: the role of 'omics' and biomarkers.

    Science.gov (United States)

    Pearson, E R

    2016-06-01

    Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide-1 receptor agonists, and thiazolidinediones are more effective in insulin-resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity-onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 (OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome-wide approaches and the potential of other 'omics', including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments. PMID:26802434

  7. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study.

    Science.gov (United States)

    Gaillard, Romy; Steegers, Eric A P; Duijts, Liesbeth; Felix, Janine F; Hofman, Albert; Franco, Oscar H; Jaddoe, Vincent W V

    2014-04-01

    Maternal prepregnancy obesity is associated with impaired cardiometabolic health in offspring. Whether these associations reflect direct intrauterine causal mechanisms remains unclear. In a population-based prospective cohort study among 4871 mothers, fathers, and their children, we examined the associations of both maternal and paternal prepregnancy body mass index (BMI) with childhood body fat distribution and cardiometabolic outcomes and explored whether any association was explained by pregnancy, birth, and childhood factors. We measured childhood BMI, total body and abdominal fat distribution, blood pressure, and blood levels of lipids, insulin, and C-peptide at the age of 6 years. We observed that higher maternal and paternal prepregnancy BMI were associated with higher childhood BMI, total body and abdominal fat mass measures, systolic blood pressure, and insulin levels and lower high-density lipoprotein cholesterol levels (Pobese mothers had increased risks of childhood overweight (odds ratio, 3.84 [95% confidence interval, 3.01-4.90]) and clustering of cardiometabolic risk factors (odds ratio, 3.00 [95% confidence interval, 2.09-4.34]). Smaller effect estimates for these outcomes were observed for paternal obesity. In conclusion, higher maternal and paternal prepregnancy BMI were associated with an adverse cardiometabolic profile in offspring, with stronger associations present for maternal prepregnancy BMI. These findings suggest that maternal prepregnancy BMI may influence the cardiometabolic health of offspring through direct intrauterine mechanisms.

  8. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways.

    Directory of Open Access Journals (Sweden)

    Alessandra Baragli

    Full Text Available Availability of large amounts of in vitro generated β-cells may support replacement therapy in diabetes. However, methods to obtain β-cells from stem/progenitor cells are limited by inefficient endocrine differentiation. We have recently shown that the ghrelin gene product obestatin displays beneficial effects on pancreatic β-cell survival and function. Obestatin prevents β-cell apoptosis, preserves β-cell mass and stimulates insulin secretion in vitro and in vivo, in both normal and diabetic conditions. In the present study, we investigated whether obestatin may promote in vitro β-cell generation from mouse pancreatic islet-derived precursor cells. Treatment of cultured islets of Langerhans with obestatin (i enriched cells expressing the mesenchymal/neuronal marker nestin, which is associated with pancreatic precursors; (ii increased cell survival and reduced apoptosis during precursor selection; (iii promoted the generation of islet-like cell clusters (ICCs with increased insulin gene expression and C-peptide secretion. Furthermore, obestatin modulated the expression of fibroblast growth factor receptors (FGFRs, Notch receptors and neurogenin 3 (Ngn3 during islet-derived precursor cell selection and endocrine differentiation. These results indicate that obestatin improves the generation of functional β-cells/ICCs in vitro, suggesting implications for cell-based replacement therapy in diabetes. Moreover, obestatin may play a role in regulating pathways involved in pancreas development and regeneration.

  9. Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver.

    Science.gov (United States)

    Furrer, J; Hättenschwiler, A; Komminoth, P; Pfammatter, T; Wiesli, P

    2001-05-01

    We report a patient with a hepatic neuroendocrine tumor showing an extraordinary change of the tumor's humoral manifestations from a clinically documented extrapituitary acromegaly and a typical carcinoid syndrome toward a hyperinsulinemic hypoglycemia syndrome. At the primary manifestation of the tumor, an increased serum level of insulin-like growth factor I due to overproduction of GHRH and an increased urinary excretion of 5-hydroxyindoleacetic acid were found. The clinical manifestation of the GHRH excess was an arthralgia, which resolved completely after operative tumor debulking and normalization of insulin-like growth factor I and GHRH serum levels. The secretion of serotonin from the tumor resulted in a typical carcinoid syndrome including right-sided valvular heart disease. On the later course of the disease, the humoral manifestations of the tumor were supplemented by the secretion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia. The hepatic origin of hyperinsulinism was demonstrated by selective arterial calcium stimulation. Moreover, tumor cells revealed insulin and C-peptide immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after the initial diagnosis of the tumor, and a carefully performed autopsy procedure confirmed the absence of any extrahepatic tumor manifestation.

  10. Total pancreatectomy combined with partial pancreas autotransplantation for recurrent pancreatic cancer: a case report.

    Science.gov (United States)

    Kobayashi, T; Sato, Y; Hirukawa, H; Soeno, M; Shimoda, T; Matsuoka, H; Kobayashi, Y; Tada, T; Hatakeyama, K

    2012-05-01

    We describe a patient presenting with a resectable carcinoma of the remnant pancreas at 3 years after undergoing a pylorus-preserving pancreaticoduodenectomy for invasive ductal carcinoma of the pancreatic head. We also performed a distal pancreas autotransplantation using a part of the resected pancreas to preserve endocrine function. Final histologic findings showed the second tumor to be an invasive ductal carcinoma consisting of a well-differentiated tubular adenocarcinoma with similar histopathologic findings as the first tumor. There were no microscopic lymph node metastases and no evidence of microvascular invasion (pStage IA [pT1, pN0, M0] and R0 according to the International Union Against Cancer TNM classification). The patient was discharged at 20 days after surgery without any trouble and followed by adjuvant chemotherapy with S-1. The carbohydrate antigen 19-9 value was again normalized after the second surgery. Twenty months after the second operation, the patient is alive without cancer recurrence. The pancreas graft is functioning with a blood glucose of 108 mg/dL, HbA1C of 6.2%, and serum C-peptide of 1.4 ng/mL.

  11. Comparisons of Differentiation Potential in Human Mesenchymal Stem Cells from Wharton’s Jelly, Bone Marrow, and Pancreatic Tissues

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    Shih-Yi Kao

    2015-01-01

    Full Text Available Background. Type 1 diabetes mellitus results from autoimmune destruction of β-cells. Insulin-producing cells (IPCs differentiated from mesenchymal stem cells (MSCs in human tissues decrease blood glucose levels and improve survival in diabetic rats. We compared the differential ability and the curative effect of IPCs from three types of human tissue to determine the ideal source of cell therapy for diabetes. Methods. We induced MSCs from Wharton’s jelly (WJ, bone marrow (BM, and surgically resected pancreatic tissue to differentiate into IPCs. The in vitro differential function of these IPCs was compared by insulin-to-DNA ratios and C-peptide levels after glucose challenge. In vivo curative effects of IPCs transplanted into diabetic rats were monitored by weekly blood glucose measurement. Results. WJ-MSCs showed better proliferation and differentiation potential than pancreatic MSCs and BM-MSCs. In vivo, WJ-IPCs significantly reduced blood glucose levels at first week after transplantation and maintained significant decrease till week 8. BM-IPCs reduced blood glucose levels at first week but gradually increased since week 3. In resected pancreas-IPCs group, blood glucose levels were significantly reduced till two weeks after transplantation and gradually increased since week 4. Conclusion. WJ-MSCs are the most promising stem cell source for β-cell regeneration in diabetes treatment.

  12. Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the β-Cell Regeneration in STZ Induced Diabetic Rats.

    Science.gov (United States)

    Attanayake, Anoja Priyadarshani; Jayatilaka, Kamani Ayoma Perera Wijewardana; Pathirana, Chitra; Mudduwa, Lakmini Kumari Boralugoda

    2016-01-01

    Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating the β-cell regeneration and biosynthesis of insulin in diabetic rats. PMID:26881248

  13. Gmelina arborea Roxb. (Family: Verbenaceae Extract Upregulates the β-Cell Regeneration in STZ Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Anoja Priyadarshani Attanayake

    2016-01-01

    Full Text Available Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg and glibenclamide as the standard drug (0.50 mg/kg were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p<0.05. The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect on β-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved in G. arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg showed beneficial effects against diabetes mellitus through upregulating the β-cell regeneration and biosynthesis of insulin in diabetic rats.

  14. Positive Correlation of PTH-Related Peptide with Glucose in Type 2 Diabetes

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    Ioannis Legakis

    2009-01-01

    Full Text Available Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Recent studies indicate that for attaining a well-functioning ß-cell mass, parathyroid hormone-related protein (PTHrP is a very promising candidate among several insulinotropic peptides. In order to elucidate its role, we determine the levels of PTHrP, insulin and c-peptide in type 2 diabetics and in normal subjects in the fasting state. We enrolled 28 patients (16 men and 12 postmenopausal women with type 2 diabetes and twenty eight aged-matched healthy individuals as control subjects (15 men and 13 women. PTHrP was statistically significant correlated with glucose in type 2 diabetes and in normal subjects in the fasting state. Additionally, PTHrP serum levels exhibited a significant increase in type 2 diabetes compared to control subjects. Interestingly, PTHrP showed a positive correlation with insulin levels only among healthy individuals presumably due to defective glucose stimulated insulin secretion known to occur in type 2 diabetics. In conclusion ,the strong positive relation of PTHrP with glucose in the fasting state in patients with type 2 diabetes mellitus raises several questions for further experimentation concerning its exact role and physiological significance.

  15. Surface Modification of Biomimetic PLGA-(ASP-PEG) Matrix with RGD-Containing Peptide: a New Non-Viral Vector for Gene Transfer and Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    GUO Xiaodong; SONG Yulin; ZHENG Qixin; YANG Shuhua; SHAO Zengwu; WU Yongchao; HAO Jie; QUAN Daping

    2006-01-01

    RGD-containing peptide (K16-GRGDSPC), characterized as non-viral gene vectors, was fabricated to modify the surface of PLGA-[ASP-PEG] matrix, which offered the foundation for gene transfer with porous matrix of gene activated later. Peptide was synthesized and matrix was executed into chips A,B and chip C. Chip C was regarded as control. Chips A and B were reacted with cross-linker. Then chip A was reacted with peptide. MS and HPLC were used to detect the MW and purity of peptide. Sulphur, existing on the surface of biomaterials, was detected by XPS. The purity of un-reacted peptide in residual solution was detected by a spectrophotometer. HPLC shows that the peptide purity was 94%-95%, and MS shows that the MW was 2 741.3307. XPS reveals that the binding energy of sulphur was 164 eV and the ratio of carbon to sulphur (C/S) was 99.746∶0.1014 in reacted chip A. The binding energy of sulphur in reacted chip B was 164 eV and 162 eV, C/S was 99.574∶0.4255, and there was no sulphur in chip C. Peptide was manufactured and linked to the surface of biomimetic and 3-D matrix, which offered the possibilities for gene transfer and tissue engineering with this new kind of non-viral gene vector.

  16. PlanHab: the combined and separate effects of 16 days of bed rest and normobaric hypoxic confinement on circulating lipids and indices of insulin sensitivity in healthy men.

    Science.gov (United States)

    Simpson, Elizabeth J; Debevec, Tadej; Eiken, Ola; Mekjavic, Igor; Macdonald, Ian A

    2016-04-15

    PlanHab is a planetary habitat simulation study. The atmosphere within future space habitats is anticipated to have reduced Po2, but information is scarce as to how physiological systems may respond to combined exposure to moderate hypoxia and reduced gravity. This study investigated, using a randomized-crossover design, how insulin sensitivity, glucose tolerance, and circulating lipids were affected by 16 days of horizontal bed rest in normobaric normoxia [NBR: FiO2 = 0.209; PiO2 = 133.1 (0.3) mmHg], horizontal bed rest in normobaric hypoxia [HBR: FiO2 = 0.141 (0.004); PiO2 = 90.0 (0.4) mmHg], and confinement in normobaric hypoxia combined with daily moderate intensity exercise (HAMB). A mixed-meal tolerance test, with arterialized-venous blood sampling, was performed in 11 healthy, nonobese men (25-45 yr) before (V1) and on the morning ofday 17of each intervention (V2). Postprandial glucose and c-peptide response were increased at V2 of both bed rest interventions (PHypoxia did not alter the adverse effects of bed rest on insulin sensitivity and glucose tolerance but appeared to increase insulin clearance. The negative effect of bed rest on HDL was compounded in hypoxia, which may have implications for long-term health of those living in future space habitats. PMID:26769956

  17. Serum adiponectin concentrations in patients with essential hypertension

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-ping; YANG Cheng-ti; GAO Xing-yu; ZHANG Ling; HU Hou-xiang; CHEN Li

    2004-01-01

    To explore the serum levels of adiponectin in patients with essential hypertension and the relationbetween adiponectin and blood pressure. Methods: Forty-five cases with essential hypertension and 43 healthy control sub-jects have been taken fasting blood samples for measurements of plasma glucose, plasma lipids, insulin, C-peptide, thyroidhormones, TNF-α, leptin and adiponectin. Glucose tolerance was assessed by 75-g oral glucose tolerance est. Results: Theconcentrations of adiponectin in cases with essential hypertension were significantly lower than those in the control group(4.15 ± 1.99 vs 7.04 ± 3.13 mg/ml, P = 0.000). Pearson relation analysis showed that serum adiponectin concentrationswere negatively and significantly correlated with body-mass index ( r = - 0. 274, P = 0. 038 ), total cholesterol(r = -0.257, P = 0.048)in control groups, while adiponectin concentrations were negatively and significantly correlatedwith systolic blood pressure ( r = - 0.356, P = 0.016), triglyceride ( r = - 0.367, P = 0.013), tumor necrosis factor-al-pha ( r = - 0. 298, P = 0.047) and triiodothyronine ( r = - 0.317, P = 0. 034) in essential hypertension group. Multipleregression analysis showed that body-mass index was the independent factor to adiponectin levels, and SBP and TNF-α wereadiponectin independent factors in the essential hypertension group. Conclusion: The serum adiponectin concentrations aresignificant lower in patients with essential hypertension, and there is negative and significantly correlation between adiponec-tin and blood pressure.

  18. The investigation of intercostal Somatosensory Evoked Potentials in senile patients with diabetes

    Institute of Scientific and Technical Information of China (English)

    Xu lanping; pan yonghua; lu weihong; wu yue; zhou lichun

    2000-01-01

    Objective: To explove intercostal Somatosensory evoked potcntials(ISEP)and MEP,SEP,BAEP,ECoG,VEP in the evaluation on senile patients with DM Methods:fffth-tvo neurologialy normal subjects and 35 senile patients with clinic ally definited Dm were used in this inrestigation to general intercostal SEPs were studied.It is that the stimulation site for the fifth,seventh and nineth intercostal nervcs is at the anterior axillary line, whereas the third intercostal nerve is excited just lateral to the stemum. Result:.ISEP latency date(X+2.5SD),ISEP side to side analysis, T test of ISEP in normal compared with diabetes, β cell function in 35 senile patients with DM were compared with plasma glucose,Ralation between ISEP and other multimodal evoked potential,the abnormal rate of ISEP26 case .Respectively comparison of ISEP between DM patients with healths controlsexcept LN3 RN3 LN9 t=0.147-1.57,p=0.22-1.gl,the others were t=2.3-7.3,p=0. 000-0.02.The ISEPresult were comparedwith FPG, PPG、 HbAlc,disease duration,insulin. C peptid r=0.243-0.905,p=0.0l-0.05.Conclusion:ISEP could evaluate sternum lesions affecting the thoracic nerve roots disease,but also might be help in judging peripheral nerve disease with DM early diagnosis and predict the course of the disease.

  19. WJD 5th Anniversary Special Issues(3): Type 1 diabetes Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Elena; Pipi; Marietta; Marketou; Alexandra; Tsirogianni

    2014-01-01

    Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.

  20. [Detections of hepatitis C virus RNA and NS3 antigen and their relation to liver histopathology].

    Science.gov (United States)

    Wang, F; Wang, S; Jin, L

    1995-11-01

    To detect the distribution of hepatitis C virus and investigate the pathogenesis mechanisms of the viral infection in the liver tissues of the patients with acute or chronic hepatitis C, we examined HCV antigen expression by using the murine monoclonal antibody against HCV C33c peptide in the paraffin-embedded liver tissues from 28 patients with acute or chronic hepatitis C. The NS3 antigen was detected in 85.7% (24/28) of all the biopsy specimens. The distribution and staining density of the antigen immunoreactive signal varied according to different types of patients and the regions in the liver sections, but they obviously had a topographical relationship with the inflammatory-necrosis areas such as fatty and ballooning degeneration and focal necrosis in the liver tissues of nearly all the patients. In addition, the localization of HCV RNA investigated by in situ hybridization assay in 20 liver tissues the above 28 biopsy HD in the Chinese. They also provide valuable data for HD molecular diagnosis, genetic counselling and genetic health. PMID:8697087

  1. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells

    Institute of Scientific and Technical Information of China (English)

    Donghui Zhang; Wei Jiang; Meng Liu; Xin Sui; Xiaolei Yin; Song Chen; Yan Shi; Hongkui Deng

    2009-01-01

    Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDX1-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insulin-producing cells. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.

  2. Prognostic value of endothelial dysfunction in type 1 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ana; Marice; Ladeia; Raphael; Ribeiro; Sampaio; Maiara; CostaHita; Luis; F; Adan

    2014-01-01

    Patients with diabetes mellitus are at high risk of developing atherosclerosis, associated with higher rates of micro and macro vascular involvement such as coronary artery disease and renal disease. The role of hyperglycemia to induce synthesis of reactive oxygen species by the oxidation of glucose, leading to an increased production of advanced glycosylation end products, as well as inflammation and oxidative stress has been proposed as a possible mechanism in the pathogenesis of endothelial dysfunction(ED). The interaction between C-peptide- the connecting segment of pro-insulin-and nitric oxide in vasodilation is also discussed. Therefore, endothelial dysfunction has been identified as an early marker of vascular disorder in type 1 and type 2 diabetes mellitus. In some other diseases, ED has been considered an independent predictor of vascular disease, regardless of the method used. Studies have demonstrated the importance of endothelial dysfunction as an useful tool for identifying the risk of vascular complications in patients with type 1 diabetes mellitus, particularly as regards to renal impairment. The aim of this review is to clarify the prognostic value of endothelial dysfunction as a marker of vascular disease in these subjects.

  3. Glycemic and lipid metabolic disorders in diabetic and non-diabetic patients bmi 35 before gastric bypass

    Directory of Open Access Journals (Sweden)

    Manuel Garciacaballero

    2014-05-01

    Full Text Available Introduction: Obesity and diabetes are diseases with high prevalence worldwide. There is currently no effective medical treatment for combat the weight gain. It is precursor of diseases such as diabetes or metabolic syndrome. It is necessary to know if weight gain has cumulative effects on the glycemic and lipid metabolism as precursors of complications or comorbidities. Patients and methods: We studied 131 patients (78 nondiabetic and 53 diabetic, 37 BMI 35 (81 BMI 35-49.9 and 13 BMI > 50. We analyzed BMI, gender, diabetes and the time of evolution. Lipid profile, glucose, HbA1c and C-peptide evaluated after 12-hour fasting. Results: Diabetic and diabese patients showed high triglycerides. Non-diabetics have impaired glucose (58% BMI 35. The 20% of non-diabetics BMI 35 had high levels. The 5% of diabetics BMI 35 had high levels. HbA1c was higher in 40% of non-diabetic patients BMI 35. Conclusions: Glucose and triglycerides increase with age and years of development of T2DM. Age of 51 and more, and men are more affected. The weight increase has cumulative effect by altering the metabolism favoring the onset of diabetes and comorbidities. Despite having intensive control treatment of diabetes, it continues its deleterious effects on patients through the years.

  4. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  5. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    Science.gov (United States)

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus. PMID:24385073

  6. Antidiabetic Effects of Yam (Dioscorea batatas) and Its Active Constituent, Allantoin, in a Rat Model of Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Go, Hyeon-Kyu; Rahman, Md Mahbubur; Kim, Gi-Beum; Na, Chong-Sam; Song, Choon-Ho; Kim, Jin-Shang; Kim, Shang-Jin; Kang, Hyung-Sub

    2015-10-01

    The objective of this study was to investigate the therapeutic efficacies of crude yam (Dioscorea batatas) powder (PY), water extract of yam (EY), and allantoin (the active constituent of yam) in streptozotocin (STZ)-induced diabetic rats with respect to glucose, insulin, glucagon-like peptide-1 (GLP-1), C-peptide, glycated hemoglobin (HbAlc), lipid metabolism, and oxidative stress. For this purpose, 50 rats were divided into five groups: normal control (NC), diabetic control (STZ), and STZ plus treatment groups (STZ + PY, STZ + EY, and STZ + allantoin). After treatment for one-month, there was a decrease in blood glucose: 385 ± 7 in STZ, 231 ± 3 in STZ + PY, 214 ± 11 in STZ + EY, and 243 ± 6 mg/dL in STZ + allantoin, respectively. There were significant statistical differences (p yam and allantoin have antidiabetic effects by modulating antioxidant activities, lipid profiles and by promoting the release of GLP-1, thereby improving the function of β-cells maintaining normal insulin and glucose levels. PMID:26501316

  7. Combined application of OGTT, IRT and CPRT for diagnosis and treatment of type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Objective: To assess the value of combined clinical application of oral glucose tolerance test (OGTT), insulin release test (IRT) and C-peptide release test (CPRT) for the diagnosis and treatment of type 2 diabetes mellitus (DM2). Methods: Retrospect analysis of the data of the results of these three tests in 217 subjects examined was performed. Results: (1) Among the 217 subjects, 71 of them were not diagnosed as diabetics. However, upon further scrutinization of the data, 49 (69%) should be classified as diabetics. Fasting blood sugar (FPG) levels were normal in 53% of the 49, but 2h PG levels were mostly elevated with the exception of only 4 (4/49, 8%), Therefore, 2h PG levels were much more useful for screening of diabetes than FPG levels were. (2) Treatment result in these patients was not very satisfactory: only 24% of the patients (35/146) had their disease well-controlled. Conclusion: Combined clinical application of OGTT, ITR and CPRT would enhance the diagnostic accuracy of diabetes with fewer cases missed. (authors)

  8. The lack of long-range negative correlations in glucose dynamics is associated with worse glucose control in patients with diabetes mellitus.

    Science.gov (United States)

    Ogata, Hitomi; Tokuyama, Kumpei; Nagasaka, Shoichiro; Tsuchita, Takeshi; Kusaka, Ikuyo; Ishibashi, Shun; Suzuki, Hiroaki; Yamada, Nobuhiro; Hamano, Kumiko; Kiyono, Ken; Struzik, Zbigniew R; Yamamoto, Yoshiharu

    2012-07-01

    Glucose dynamics measured in ambulatory settings are fluid in nature and exhibit substantial complexity. We recently showed that a long-range negative correlation of glucose dynamics, which is considered to reflect blood glucose controllability over a substantial period, is absent in patients with diabetes mellitus. This was demonstrated using detrended fluctuation analysis (DFA), a modified random-walk analysis method for the detection of long-range correlations. In the present study, we further assessed the relationships between the established clinical indices of glycemic or insulinogenic control of hemoglobin A(1c) (HbA(1c)), glycated albumin (GA), 1,5-anhydroglucitol, and urine C-peptide immunoreactivity and the recently proposed DFA-based indices obtained from continuous glucose monitoring in 104 Japanese diabetic patients. Significant correlations between the following parameters were observed: (1) HbA(1c) and the long-range scaling exponent α(2) (r = 0.236, P control as clinically determined using HbA(1c) and GA parameters.

  9. Studies on Androgen Receptor mRNA expression in Pancreas, Hypothalamus and Ovary of Androgen Sterilized Rats

    Institute of Scientific and Technical Information of China (English)

    Li WANG; Jing-wen HOU; Li-min LU; Jin YU; Sui-qi GUI

    2004-01-01

    Objective To investigate the androgen receptor (AR) mRNA expression in pancreas,hypothalamus and ovary of androgen sterilized rats (ASR)Methods ASR model was established by subcutaneous injection of testosterone propionate to SD female rats at the age of 9 days. Around the age of 106 days (proestrus),all rats were killed, serum △ 4-andronestedione (△ 4-A), total testosterone (TT), free testosterone (FT), insulin (Ins) and C-peptide (C-P)were measured by radioimmunoassay (RIA). Total RNA in pancreas, hypothalamus and ovary were extracted and the amount of AR mRNA was quantitatedly analyzed by RT-PCR with single base mutant template as inner standard. Results Serum concentrations of△ 4-A, TT, FT, Ins and C-P in ASR model rats were significantly higher than those in control group (P<0. 05, P<0. 01). The expression of AR mRNA in pancreas, hypothalamus and ovary increased significantly (P<0. 05,P<0. 01) of model rats as compared with control group. Conclusion The elevated serum androgen levels in ASR model could enhance the expression of AR mRNA levels in pancreas, hypothalamus and ovary, which further induce hyperinsulinemia and anovulation.

  10. Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Yuan-Yuan Lv; Bing-Yin Shi; Hui Guo

    2008-01-01

    We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion deficiency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy,the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period ofIFN therapy. Type 1 DM induced by IFN-α is relativelyrare in patients with chronic hepatitis B. We should paymore attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.

  11. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

    1988-09-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

  12. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    International Nuclear Information System (INIS)

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

  13. Generation and characterization of human insulin-releasing cell lines

    Directory of Open Access Journals (Sweden)

    Joffé Elisa

    2009-06-01

    Full Text Available Abstract Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction.

  14. Generation and characterization of human insulin-releasing cell lines

    Science.gov (United States)

    Labriola, Leticia; Peters, Maria G; Krogh, Karin; Stigliano, Iván; Terra, Letícia F; Buchanan, Cecilia; Machado, Marcel CC; Joffé, Elisa Bal de Kier; Puricelli, Lydia; Sogayar, Mari C

    2009-01-01

    Background The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. Results We generated ex-vivo primary cultures from two independent human insulinomas and from a human nesidioblastosis, all of which were cultured up to passage number 20. All cell lines secreted human insulin and C-peptide. These cell lines expressed neuroendocrine and islets markers, confirming the expression profile found in the biopsies. Although all beta cell lineages survived an anchorage independent culture, none of them were able to invade an extracellular matrix substrate. Conclusion We have established three human insulin-releasing cell lines which maintain antigenic characteristics and insulin secretion profiles of the original tumors. These cell lines represent valuable tools for the study of molecular events underlying beta cell function and dysfunction. PMID:19545371

  15. Human insulin dynamics in women: a physiologically based model.

    Science.gov (United States)

    Weiss, Michael; Tura, Andrea; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2016-02-01

    Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake. PMID:26608654

  16. Human islets and dendritic cells generate post-translationally modified islet autoantigens.

    Science.gov (United States)

    McLaughlin, R J; de Haan, A; Zaldumbide, A; de Koning, E J; de Ru, A H; van Veelen, P A; van Lummel, M; Roep, B O

    2016-08-01

    The initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neoepitope formation indicate that post-translational modification of islet autoantigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamidation of islet autoantigens increases their binding affinity to the T1D highest-risk human leucocyte antigen (HLA) haplotypes HLA-DR3/DQ2 and -DR4/DQ8, increasing the chance that T cells reactive to deamidated autoantigens can be activated upon T cell receptor ligation. Here we investigated human pancreatic islets and inflammatory and tolerogenic human dendritic cells (DC and tolDC) as potential sources of deamidated islet autoantigens and examined whether deamidation is altered in an inflammatory environment. Islets, DC and tolDC contained tissue transglutaminase, the key enzyme responsible for peptide deamidation, and enzyme activity increased following an inflammatory insult. Islets treated with inflammatory cytokines were found to contain deamidated insulin C-peptide. DC, heterozygous for the T1D highest-risk DQ2/8, pulsed with native islet autoantigens could present naturally processed deamidated neoepitopes. HLA-DQ2 or -DQ8 homozygous DC did not present deamidated islet peptides. This study identifies both human islets and DC as sources of deamidated islet autoantigens and implicates inflammatory activation of tissue transglutaminase as a potential mechanism for islet and DC deamidation. PMID:26861694

  17. Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

    International Nuclear Information System (INIS)

    We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP

  18. Differentiation of insulin-producing cells from human neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuichi Hori

    2005-04-01

    Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

  19. Specific and direct proinsulin radioimmunoassay for the evaluation of insulinomas

    International Nuclear Information System (INIS)

    The paper describes a highly specific human proinsulin (hPI) radioimmunoassay (RIA) developed by using biosynthetic hPI as immunogen, standard and tracer. Proinsulin was radioiodinated by the iodogen method and purified on QAE-Sephadex A-25 to a specific activity of 6.5 MBq/μg. The antiserum was raised in a guinea pig and then adsorbed against insulin and C-peptide conjugate to Sepharose to improve its specificity. The range of the standard curve extended from 0.004 to 16 pmol/mL, with a 50% displacement between 0.19-0.26 pmol/mL and the minimal detectable concentration between 0.01-0.04 pmol/mL. This sensitive and specific RIA proved suitable for measurements of serum hPI concentrations in patients with insulinomas, which levels ranged from 0.11 to 1.80 pmol/mL (n = 8). (author). 18 refs, 6 figs, 1 tab

  20. Insulin secretion and glucose uptake by isolated islets of the hamster

    International Nuclear Information System (INIS)

    Isolated pancreatic islets of normal hamsters were perfused either in a closed or in a open system. When the buffer was recirculated and the endogenous insulin was allowed to accumulate, the islets secreted significantly less insulin than when the system was open and the endogenous insulin was washed away. The addition of monocomponent insulin or of proinsulin to the perfusion buffer significantly decreased insulin secretion. The inhibitory action of proinsulin was significantly greater than that of monocomponent insulin. C peptide had no effect. When pancreatic islets were incubated in a fixed volume of stationary buffer containing unlabeled glucose (1.0 mg or 3.0 mg/ml) and glucose-U-14C (1.0 μC/ml), the amount of insulin secreted and the 14CO2 produced by each islet decreased progressively as the number of islets in the sample increased. Under these conditions, the concentration of insulin required to inhibit insulin secretion increased with the concentration of glucose in the medium. Proinsulin did not alter the incorporation of leucine-4.5-3H into total extractable insulin (insulin + proinsulin). Thus, insulin and proinsulin appear to inhibit insulin release, but not insulin synthesis. (orig.)