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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 produced by the body and insulin injected ...

  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. 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...

  9. 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...... 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-peptide......) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved...

  10. 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)

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19.  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.

  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. 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)

  5. 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.

  6. 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...

  7. 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

    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 was...

  8. 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

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. 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

  14. 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.)

  15. 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

    Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did n...

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Fundamental studies on the development of C-peptide radioimmunoassay kit

    International Nuclear Information System (INIS)

    We have studied the development of the C-peptide radioimmunoassay kit which is usable in the pancreatic function test with satisfactory results. The C-peptide antiserum was prepared by immunizing rabbits with synthetic human connecting peptide. The antiserum revealed no cross reaction with any C-peptides other than human C-peptide, porcine insulin and gastrointestinal hormone, and showed high specificity to human C-peptide. We adopted the double antibody method in B,F separation, and chose 40C, 48 hrs. for 1st. incubation and 40C, 24 hrs. for 2nd. incubation. On this kit, the assay range was 0.5 ng/ml-30 ng/ml, the recovery rate was 98.4%-107.8% in the recovery test, the coefficient of variance was 6.2% in the intra assay and was 7.6% in the inter assay. We think this kit is sufficiently usable to assay C-peptide in blood. (auth.)

  2. C-peptide comparative radioimmunoassays: a study of three commercial kits

    International Nuclear Information System (INIS)

    Plasma C-peptide immunoreactivity (CPR) was measured in 18 fasting subjects with three different commercial kits (RIA-mat C-peptide-, Byk-Mallinckrodt; RIA-gnost-hC-peptide, Hoechst-Behring; human C-peptide radioimmunoassay kit, Novo) The subjects were chosen as to cover a wide range of CPR concentrations (five healthy subjects, six obese subjects, three insulin-dependent diabetics, four normal subjects whose plasmas had been kept at - 200C for periods of 16 or 36 months). CPR was measured with the Novo kit in eight other plasmas which were kept over a period of 36 months, with or without aprotinin. Good correlations have been established among the values found with the three kits. However, absolute concentration values for each subject as well as the dispersion of all plasma C-peptide values varied as a function of the kit used because of antibody specificity differences and because of the various separation methods. The normal range proposed changes with each kit and the blood CPR of a subject can be a normal, reduced or increased one, depending on the kit used. After several months of storage, plasma CPR degradation is observed with the three kits. A protease-inhibitor is necessary in order to avoid this C-peptide degradation due to the apparent existence of a plasma proteolytic enzyme

  3. 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.

  4. 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...... disorders, four had cirrhosis without organic kidney disease, and four had organic kidney disease with moderately decreased glomerular filtration rate. In subjects without organic kidney disease the arteriorenal venous extraction ratios of insulin, C-peptide, and proinsulin were mean 0.27, 0.20, and 0.......21, respectively (n = 14). These values were significantly reduced in kidneys with organic disease. Renal plasma clearance values of insulin, C-peptide, and proinsulin were mean 113, 87, and 90 mL/min, respectively (n = 6). Urinary clearances were substantially lower (0.8, 13, 3.5 mL/min, respectively), indicating...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. 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

  10. 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

  11. 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

  12. A study on the C-peptide radioimmunoassay with synthetized connecting peptide

    International Nuclear Information System (INIS)

    A method of C-peptide radioimmunoassay with the synthetized connecting peptide by Yanaihara was tested for the determination of serum C-peptide immunoreactivity (CPR) in normal people and in diabetics with or without insulin treatment. The CPR value obtained by this method was not interfered with by the presence of serum proteins or by the insulin of people with or without insulin treatment judged by the dilution test and the recovery test. The normal fasting CPR was 2.80 +- 0.78 ng/ml with the synthetized C-peptide as a standard. The CPR value increased and reached a maximum 90 minutes after the ingestion of 50 g of glucose. The increase after the glucose loading reduced corresponding to the severity of diabetes, and some juvenile-onset diabetes showed no response. Adult-type diabetics under insulin treatment, however, showed weak but significant CPR response. The increment of CPR and immunoreactive insulin after glucose loading in normal people and non-treated diabetics was well correlated (γ=0.8262). Judged from the above mentioned results, CPR determination in insulin-treated diabetics was thought to be a useful method for the assessment of the insulin-secreting ability of beta-cells of the pancreas. (J.P.N.)

  13. 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.

  14. 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...

  15. Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes

    OpenAIRE

    Montalcini, T; Gallotti, P.; Coppola, A; Zambianchi, V.; Fodaro, M.; Galliera, E.; Marazzi, M G; S. Romeo; Giannini, S.; Corsi Romanelli, M. M.; Pujia, A; Gazzaruso, C

    2015-01-01

    Summary In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. Introduction It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the p...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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)

  18. 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)

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

    OpenAIRE

    Sung-Tae Kim; Byung-Joon Kim; Dong-Mee Lim; In-Geol Song; Jang-Han Jung; Kang-Woo Lee; Keun-Young Park; Youn-Zoo Cho; Dae-Ho Lee; Gwan-Pyo Koh

    2011-01-01

    Background Recent 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. Methods Data 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 c...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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

  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...... limit, 49 of 125 patients were without residual insulin secretion. In contrast to this, only 7 patients were diagnosed as C-peptide nonsecretors using the analytical detection limit of urinary C-peptide. Eighty-four per cent of patients considered to have Type 1 (insulin-dependent) diabetes with a...... consecutive 24-h urine specimens and related to plasma C-peptide 6 min after the intravenous injection of 1 mg glucagon. The detection limit of C-peptide in plasma was defined analytically (greater than or equal to 0.02 nmol l-1) and from pancreatectomized patients (greater than or equal to 0.06 nmol l-1...

  4. 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 is...... insulin-producing cells showed highly differential expression at the cellular level of the three proinsulin C-peptide immunoreactivities, as follows: C-peptide I greater than human C-peptide greater than C-peptide II. The fractions of cells expressing human C-peptide and C-peptide II decreased in time and...... species of proinsulin-C-peptide immunoreactivity but still at high levels. However, rat C-peptide II and human C-peptide were often colocalized, even in later passages. In situ hybridization studies combined with the immunocytochemical data suggest that the differential expression occurs at the level of...

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Canine C-peptide for characterization of experimental diabetes in dogs

    International Nuclear Information System (INIS)

    Radioimmunoassay of canine C-peptide (CCP) was developed for the characterization of endogenous beta cell function in experimentally diabetic dogs. The animals were rendered diabetic by subtotal pancreatectomy and intrasurgical infusion of 2 mg/kg streptozotocin into the superior pancreaticoduodenal artery. After an average duration of diabetes of 5 months the animals showed zero peripheral venous fasting CCP levels with no response to feeding, OGTT/i.v. glucagon loading or i.v. glucose tolerance testing. The data on CCP levels entirely coincided with simultaneously measured plasma IRI levels. In non-diabetic control animals clear-cut CCP increases were observed after all stimuli. The experimental model provided an IDDM-type diabetes without toxic symptoms but with a sufficient exocrine pancreatic function. The comparison showed that plasma IRI analyses would also allow reliable characterization of insulinogenic functions in these animals. (author)

  11. 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.

  12. 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...

  13. 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...

  14. Hypertension association with serum lipoproteins, insulin, insulin resistance and C-peptide: Unexplored forte of cardiovascular risk in hypothyroidism

    Directory of Open Access Journals (Sweden)

    Purvi Purohit

    2013-01-01

    Full Text Available Background: There is a gross dearth of correlative data for cardiovascular diseases. Aim: We aimed to explore the association of systolic and diastolic blood pressure with anthropometric and biochemical parameters of hypothyroid patients in order to establish any correlation that may exist and be useful in an early diagnosis and management against cardiovascular risk. Materials and Methods: The study included 100 healthy controls and 150 newly diagnosed hypothyroid patients. Subjects were evaluated anthropometrically and biochemically for fasting blood sugar, triiodothyronine, thyroxine, thyroid stimulating hormone, Insulin, C-peptide, lipid profile, apo-B and apo-A 1 . The results were statistically analysed using unpaired t-test and Spearman′s coefficient of Correlation. Results: The hypothyroids had a female preponderance (73.3% however; their biochemical profiles were comparable with those of male counterparts. They had raised Body Mass Index, hypertension, hyperinsulinemia, insulin resistance, raised C-peptide, dyslipidaemia with raised apo-B and reduced apo-A 1 and strong association of systolic and diastolic blood pressure with insulin, insulin resistance, C-peptide and Total cholesterol/HDLc (TC/HDLc. Conclusion: Strong association of hypertension with serum insulin, IR, C -peptide and TC/HDLc hints significant contribution towards cardiovascular risk in hypothyroid adults of Jodhpur.

  15. 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…

  16. 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

  17. 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...

  18. Postprandial C-Peptide to Glucose Ratio as a Marker of β Cell Function: Implication for the Management of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Yoshifumi Saisho

    2016-05-01

    Full Text Available C-peptide is secreted from pancreatic β cells at an equimolar ratio to insulin. Since, in contrast to insulin, C-peptide is not extracted by the liver and other organs, C-peptide reflects endogenous insulin secretion more accurately than insulin. C-peptide is therefore used as a marker of β cell function. C-peptide has been mainly used to assess the presence of an insulin-dependent state for the diagnosis of type 1 diabetes. However, recent studies have revealed that β cell dysfunction is also a core deficit of type 2 diabetes, and residual β cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. This review summarizes the role of C-peptide, especially the postprandial C-peptide to glucose ratio which likely better reflects maximum β cell secretory capacity compared with the fasting ratio in assessing β cell function, and discusses perspectives on its clinical utility for managing glycemic control in patients with type 2 diabetes.

  19. A Study of the Insulin and the C-Peptide Responses to Oral Glucose Load in Nondiabetic and Diabetic Subjects

    International Nuclear Information System (INIS)

    The present study was undertaken to evaluate the significance of the insulin and the C-peptide response to oral glucose loads in normal and diabetic subjects and to establish the effects of the obesity. In this study, the authors have measured plasma insulin and C-peptide by means of radioimmunoassay in 10 nonobese normal, 5 obese normal, 13 nonobese moderate diabetic patients, 9 obese moderate diabetic patients and 9 severe diabetic patients. The results obtained were as follows; 1) In 10 nonobese normal subjects, the plasma insulin level at fasting state and at 30, 60, 90, and 120 min after oral glucose loads were 15.7±3.4, 48.3±9.8, 40.4±6.7, 37.4±6.5 and 26.0±4.2 uU/ml (Mean±S.E.) and C-peptide were 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 and 4.0±0.5 ng/ml. The change of C-peptide was found to go almost parallel with that of insulin and the insulin value reaches to the highest level at 30 min whereas C-peptide reaches to its peak at 60 min.. 2) The plasma insulin level in 5 obese normal subjects were 38.9±12.3, 59.5±12.3, 59.2±17.1, 56.1±20.0 and 48.4±17.2 uU/ml and the C-peptide were 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 and 7.8±2.0 ng/ml. The insulin response appeared to be greater than nonobese normal subjects. 3) In 13 nonobese moderate diabetic patients, the plasma insulin levels were 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 and 34.7±10.7 uU/ml and the C-peptide levels were 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 and 6.7±1.0 ng/ml. There was little significance compared to nonobese normal groups but delayed pattern is noted. 4) In 9 obese moderated diabetic patients, the plasma insulin levels were 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 and 55.5±10.l uU/ml and the C-peptide levels were 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 and 10.1±1.0 ng/ml and its response was also greater than that of nonobese moderate diabetic patients. 5) The plasma insulin concentrations in 9 severe diabetic subjects were 8.0±3.8, 12.1±3.5, 16.8±4.6, 19

  20. 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

  1. 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

  2. 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...

  3. The association between newborn regional body composition and cord blood concentrations of C-peptide and insulin-like growth factor I

    DEFF Research Database (Denmark)

    Carlsen, Emma M; Renault, Kristina M; Jensen, Rikke B; Nørgaard, Kirsten; Jensen, Jens-Erik Beck; Nilas, Lisbeth; Cortes, Dina; Michaelsen, Kim F.; Pryds, Ole

    2015-01-01

    associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I. METHODS: 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...... 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...

  4. 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.

  5. 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.

  6. Deleting the Redundant TSH Receptor C-Peptide Region Permits Generation of the Conformationally Intact Extracellular Domain by Insect Cells.

    Science.gov (United States)

    Chen, Chun-Rong; Salazar, Larry M; McLachlan, Sandra M; Rapoport, Basil

    2015-07-01

    The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine-rich repeat domain and an hinge region (HR), the latter contributing to ligand binding and critical for receptor activation. The crystal structure of the leucine-rich repeat domain component has been solved, but previous attempts to generate conformationally intact complete ECD or the isolated HR component for structural analysis have failed. The TSHR HR contains a C-peptide segment that is removed during spontaneous TSHR intramolecular cleavage into disulfide linked A- and B-subunits. We hypothesized that deletion of the redundant C-peptide would overcome the obstacle to generating conformationally intact TSHR ECD protein. Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the isolated HR (termed HR-D1) were secreted into medium of insect cells infected with baculoviruses coding for these modified proteins. The identities of TSHR ECD-D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required a multistep protocol with a low yield. In conclusion, we report a novel approach to generate the TSHR ECD, as well as the isolated HR in insect cells, the former in sufficient amounts for structural studies. However, such studies will require previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating antibody. PMID:25860033

  7. 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

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Estimation of serum insulin, Homeostasis model assessment-insulin resistance and C-peptide can help identify possible cardiovascular disease risk in thyroid disorder patients

    Directory of Open Access Journals (Sweden)

    Purvi Purohit

    2012-01-01

    Full Text Available Aim: We aimed at evaluating the cardiovascular disease (CVD risk of thyroid disorder patients at diagnosis, using the traditional lipid profile, apo-B and apo-A1 in correlation with serum insulin and insulin resistance (IR and C-peptide. Background: With an ever increasing incidence of CVD in most urban populations, there has been a demand for newer techniques that could help in the early detection of the risk of this disease complex. Materials and Methods: The present study was conducted on 100 healthy controls and 150 hypothyroid and 70 hyperthyroid patients, coming for the first time to our OPDs. The patients were selected on the basis of symptomatology and serum T3, T4, thyroid stimulating hormone (TSH evaluations. They were then analyzed for body mass index (BMI, blood pressure (BP, serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR, C-peptide, lipid profile and apo-B and -A1. Statistical analysis was done using Student′s "t" test and Spearman′s coefficient of correlation. Results: The hypothyroid patients presented with high BMI, diastolic hypertension, dyslipidemia, hyperinsulinemia, IR and raised serum C-peptide. There was highly significant correlation of serum insulin, HOMA-IR and C-peptide with lipid fractions and CVD risk ratios, T. chol/HDLc and apo-B/apo-A1, in hypothyroid patients. The hyperthyroid patients presented with systolic hypertension and a significant correlation of T. chol/HDLc with HOMA-IR. Hyperthyroid patients also had hyperinsulinemia, but reduced serum C-peptide levels. Conclusion: We conclude that the estimation of traditional lipid profile along with serum insulin, IR, C-peptide, apo-A1 and apo-B would not only help assess the thyroid status, but can also help in the early evaluation of a possible risk of CVD.

  11. 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

  12. 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

    progression of the disease. Likewise, CCL3 was negatively related to C-peptide and positively associated with the beta-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased beta-cell stress shown by negative association with proinsulin. Blockage of chemokines or antagonism...

  13. 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, ...

  14. Analysis of changes of serum leptin, C-peptide levels and peripheral fat tissue leptin receptor expression in obesity

    International Nuclear Information System (INIS)

    Objective: To explore the mechanism of obesity and obesity accompanied type two diabetes mellitus by investigating changes of serum leptin, C-peptide (C-P) levels and leptin receptor expression in peripheral adipose tissues. Methods: Peripheral leptin receptor density was measured via radio-ligand binding method, serum leptin and C - P levels were measured via radioimmunoassay in 91 cases (38 in obesity group, 23 in over weight, and 30 in normal controls). Results: With the increase of body mass index (BMI), the peripheral leptin receptor density of the over weight and obese cases decreased and was mash less than that of normal cases (both p<0.01, respectively). There was no statistical differences for Kd value among the three groups, suggesting no associated change between the binding ability of leptin receptor to its ligand. There was a negative correlation between BMI and leptin receptor density (r = -0.70, p < 0.01). The serum leptin and C-P levels in weight excess and obese subjects with type two DM were both increased, but significantly higher in obese group than those in weight excess group (p < 0.01). The increase of C-P was much marked than that of leptin. Serum C-P level was positively correlated with BMI. Conclusion: Changes of serum leptin, C-P levels and peripheral leptin receptor expression in cases with simple obesity and obesity accompanied with type two DM were related closely with BMI. Type 2 DM in obese subjects was related with leptin resistance and insulin resistance

  15. 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.

  16. 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

  17. 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 < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM 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

  18. 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.

  19. 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

  20. 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...

  1. 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-...

  2. 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

  3. 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.

  4. 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.

  5. 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

    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...... as assessed by stimulated C-peptide the first 12 months after diagnosis in children with new onset T1D in two independent cohorts collected over a time interval of 6 years. Furthermore the purpose was to assess whether the natural history of disease has changed over time. Materials and methods: The...... International Hvidoere cohort, year 1999–2000: 275 children from 22 paediatric centers; the Danish cohort, year 2005–2006: 130 children from 4 paediatric centers. All patients went through a 90-minutes Boost-test 1, 3 (only the Danish cohort), 6, 12 months to characterize the residual betacell function. All...

  6. Urinary C-Peptide Creatinine Ratio Is a Practical Outpatient Tool for Identifying Hepatocyte Nuclear Factor 1-α/Hepatocyte Nuclear Factor 4-α Maturity-Onset Diabetes of the Young From Long-Duration Type 1 Diabetes

    OpenAIRE

    Besser, Rachel E. J.; Shepherd, Maggie H; McDonald, Timothy J; Shields, Beverley M.; Knight, Bridget A; Ellard, Sian; Hattersley, Andrew T

    2011-01-01

    OBJECTIVE Hepatocyte nuclear factor 1-α (HNF1A)/hepatocyte nuclear factor 4-α (HNF4A) maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 diabetes, and patients are inappropriately treated with insulin. Blood C-peptide can aid in the diagnosis of MODY, but practical reasons limit its widespread use. Urinary C-peptide creatinine ratio (UCPCR), a stable measure of endogenous insulin secretion, is a noninvasive alternative. We aimed to compare stimulated UCPCR in adu...

  7. 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.

  8. 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。

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Diurnal trends in responses of blood plasma concentrations of glucose, insulin, and C-peptide following high- and low-fat meals and their relation to fat metabolism in healthy middle-aged volunteers

    OpenAIRE

    Frape, D. L.; Williams, N. R.; Scriven, A J; Palmer, C. R.; OSullivan, K.; Fletcher, R. J.

    1997-01-01

    An experiment was conducted in twelve healthy middle-aged volunteers, six of each sex, with a mean BMI of 27 kg/m(2) to detect differences between morning and afternoon in postprandial blood glucose, insulin and C-peptide concentrations. These responses were measured following the consumption of isoenergetic meals that were high or low in fat content, at breakfast and at lunch. Over 4d each subject received the high-carbohydrate (L, 5.5 g mixed fat/meal) and moderately high-fat (M, 33 g mixed...

  16. 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

  17. 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

  18. Surfactant protein C peptides with salt-bridges (“ion-locks” promote high surfactant activities by mimicking the α-helix and membrane topography of the native protein

    Directory of Open Access Journals (Sweden)

    Frans J. Walther

    2014-07-01

    Full Text Available Background. Surfactant protein C (SP-C; 35 residues in lungs has a cationic N-terminal domain with two cysteines covalently linked to palmitoyls and a C-terminal region enriched in Val, Leu and Ile. Native SP-C shows high surface activity, due to SP-C inserting in the bilayer with its cationic N-terminus binding to the polar headgroup and its hydrophobic C-terminus embedded as a tilted, transmembrane α-helix. The palmitoylcysteines in SP-C act as ‘helical adjuvants’ to maintain activity by overriding the β-sheet propensities of the native sequences. Objective. We studied SP-C peptides lacking palmitoyls, but containing glutamate and lysine at 4-residue intervals, to assess whether SP-C peptides with salt-bridges (“ion-locks” promote surface activity by mimicking the α-helix and membrane topography of native SP-C. Methods. SP-C mimics were synthesized that reproduce native sequences, but without palmitoyls (i.e., SP-Css or SP-Cff, with serines or phenylalanines replacing the two cysteines. Ion-lock SP-C molecules were prepared by incorporating single or double Glu−–Lys+ into the parent SP-C’s. The secondary structures of SP-C mimics were studied with Fourier transform infrared (FTIR spectroscopy and PASTA, an algorithm that predicts β-sheet propensities based on the energies of the various β-sheet pairings. The membrane topography of SP-C mimics was investigated with orientated and hydrogen/deuterium (H/D exchange FTIR, and also Membrane Protein Explorer (MPEx hydropathy analysis. In vitro surface activity was determined using adsorption surface pressure isotherms and captive bubble surfactometry, and in vivo surface activity from lung function measures in a rabbit model of surfactant deficiency. Results. PASTA calculations predicted that the SP-Css and SP-Cff peptides should each form parallel β-sheet aggregates, with FTIR spectroscopy confirming high parallel β-sheet with ‘amyloid-like’ properties. The enhanced

  19. 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

  20. 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.

  1. 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

  2. Modelling of the TrpZip2C Peptide Unfolding and its Optical Activity

    Czech Academy of Sciences Publication Activity Database

    Horníček, Jan; Bouř, Petr

    Oxford: Diamond, 2011. s. 88-88. [CD 2011. The International Conference on Chiroptical Spectroscopy /13./. 24.07.2011-28.07.2011, Oxford] R&D Projects: GA MŠk(CZ) LH11033; GA ČR GAP208/11/0105 Grant ostatní: AV ČR(CZ) M200550902; European Reintegration Grant(XE) 230955 Institutional research plan: CEZ:AV0Z40550506 Keywords : raman * vibrational optical activity * calculations Subject RIV: CF - Physical ; Theoretical Chemistry

  3. 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

  4. Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes

    OpenAIRE

    Kuo, Jane Z.; Guo, Xiuqing; Klein, Ronald; Klein, Barbara E.; Weinreb, Robert N.; Genter, Pauline; Hsiao, Fone-Ching; Goodarzi, Mark O.; Rotter, Jerome I.; Chen, Yii-Der Ida; Ipp, Eli

    2014-01-01

    Objective Residual insulin secretion provides important protection against the development of diabetic retinopathy in type 1 diabetes. The data to support this in type 2 diabetes are unclear. We therefore tested in type 2 diabetes whether markers of residual beta-cell function are associated with the development of diabetic retinopathy, an important microvascular complication of diabetes. Design Prospective, cross-sectional, family-based study. Participants 585 Latino type 2 diabetic particip...

  5. The effect of some possible factors to c-Peptide immunoreactivity urine on the quality of results

    International Nuclear Information System (INIS)

    About 15 % of CPR-U was not correspond between two kinds of kits in the routine assay, which were produced by different pharmaceutical corps, and also it is realised that the effect of the preservative, storage condition and buffer dilutions can not be overlooked in quality control programmes. Based on these problems, following results are concluded; (1) Urine preservative: NaN3 is better than toluene. (2) Urine CPR was stable for added preservative at 4 deg C for two weeks. (3) Diluents may effect the CPR-U results, if not kept in good condition. The role of the makers in supporting improved quality in clinical laboratory tests will be expectated. (author)

  6. Human c-peptide immunoreactivity (CPR) in blood and urine - evaluation of a radioimmunoassay method and its clinical applications

    International Nuclear Information System (INIS)

    A double-antibody radioimmunoassay method, using synthetic human connecting peptide as an immunizing antigen and standard, was evaluated for clinical assay of blood and urine samples. Normal fasting blood connecting peptide immunoreacivity (CPR) was 2.45 +- 0.96 ng/ml, increasing promptly after a 50 g oral glucose load, but somewhat slower than insulin. Molar concentration of CPR exceeded that of insulin. CPR responses to glucose were subnormal in diabetics, very low in juvenile-type cases, and often poor in patients on insulin treatment. Fasting CPR levels were elevated in patients on corticosteroid treatment and with uraemia. A patient with insulin 'auto-antibody' had high serum CPR. A considerable amount of CPR appeared in urine. Normal daily excretion of CPR was 1.52 +- 0.55 μg/kg or 55.1 +- 18.2 ng/mg creatinine. Urine CPR was very low in juvenile-type diabetics, and elevated in patients on corticosteroid treatment. The results confirm that blood and urine CPR are useful measures of the endocrine pancreatic function. (orig.)

  7. 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。

  8. 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.

  9. Association of Serum C-Peptide Concentrations with Cancer Mortality Risk in Pre-Diabetes or Undiagnosed Diabetes

    OpenAIRE

    Hsu, Chih-Neng; Chang, Chia-Hsuin; Lin, Yu-Sheng; Lin, Jou-Wei; Caffrey, James L

    2013-01-01

    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 s...

  10. Maternal Testosterone Levels are Associated with C-Peptide Levels in the Mexican American Subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cohort

    OpenAIRE

    Ackerman, C. M.; Lowe, L. P.; Dyer, A R; Hayes, M G; Metzger, B E; Lowe, W. L.; Urbanek, M

    2013-01-01

    Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resista...

  11. 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。

  12. 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.

  13. 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

  14. 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

    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...... 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...

  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

    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.......002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P < 0.003) and the homeostasis model assessment insulin resistance score increased significantly, indicating a deterioration in insulin sensitivity; whereas the...

  16. 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.......002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P

  17. The beta-cell response to glucagon and mixed meal stimulation in non-insulin dependent diabetes

    DEFF Research Database (Denmark)

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

    1988-01-01

    mellitus (NIDDM). Fasting plasma C-peptide as well as the C-peptide and insulin responses to glucagon, showed similar but only modest correlations with the C-peptide response to the meal. Urinary C-peptide showed no correlation with the C-peptide response to the meal, but correlated modestly with fasting...... plasma C-peptide (r = 0.55, p less than 0.01). The C-peptide and insulin responses after meal stimulation correlated modestly inversely with HbA1. In conclusion, measurement of C-peptide in fasting state, as well as measurements of C-peptide and insulin after glucagon stimulation, only modestly predict......The aim of this study was to evaluate the correlations of the C-peptide and insulin responses after stimulation with glucagon intravenously as well as the 24-h urinary excretion of C-peptide to the C-peptide response to a standard mixed meal in 30 patients with non-insulin dependent diabetes...

  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. 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.

  20. 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

  1. Age-dependent decline of beta-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study

    DEFF Research Database (Denmark)

    Barker, A.; Lauria, A.; Schloot, N.; Hosszufalusi, N.; Ludvigsson, J.; Mathieu, C.; Mauricio, D.; Nordwall, M.; Van der Schueren, B.; Mandrup-Poulsen, Thomas; Scherbaum, W. A.; Weets, I.; Gorus, F. K.; Wareham, N.; Leslie, R. D.; Pozzilli, P.

    2014-01-01

    C-peptide secretion is currently the only available clinical biomarker to measure residual β-cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline...... over time from type 1 diabetes onset in relation to age at diagnosis, HbA1c levels and insulin dose....

  2. 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.)

  3. Insulin requirement in non-insulin-dependent diabetes mellitus: relation to simple tests of islet B-cell function and insulin sensitivity

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Pedersen, P C;

    1988-01-01

    Evaluation of simple tests of islet B-cell function and insulin sensitivity as predictors of metabolic control was performed during 3 months of insulin withdrawal in 25 insulin-treated diabetic subjects. All patients had a glucagon stimulated plasma C-peptide concentration above 0.33 nmol/l and a...... fasting plasma C-peptide concentration above 0.20 nmol/l a few days before insulin withdrawal. Insulin sensitivity was measured as the glucose disappearance rate (k) during an intravenous insulin tolerance test. Two patients were considered insulin-requiring due to high fasting blood glucose levels...... stimulated C-peptide levels and insulin sensitivity (r = 0.41, p less than 0.05). Fasting and stimulated C-peptide concentrations of 0.40 and 0.70 nmol/l, respectively, separated non-insulin-requiring patients from a group consisting of both insulin- and non-insulin-requiring patients. At these C...

  4. 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 ...

  5. 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...

  6. 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...

  7. 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. PMID:1728534

  8. 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

  9. 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.

  10. 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

  11. Use of radioimmunoassay to study secretory potentialities of β-cells in patients with insulin-independent diabetes mellitus

    International Nuclear Information System (INIS)

    The nature of insulin and C-peptides secretion in 21 patient with insulin-independent diabetes mellitus (IIDM) with different acetilating phenotype in the course of intravenous glucose loadin is studied by means of the radioimmunoassay. In all patients a different nature of insulin secretion during the first stage is revealed. In the group of fast acetilators an increase in the immuno-reactive insulin (IRI) concentration in the blood serum has been observed, more strongly pronounced in patients with accompanying obesity, whereas in the group of slow acetilators a regular decrease in the IRI level is revealed during this period. The nature of C-peptides secretion in patients with the second type of diabetes mellitus with different acetilator phenotype repeats in the main the IRI dynamics characteristic of fast and slow acetilators. In patients with IIDM with obesity belonging to fast acetilators, the nature of C-peptide secretion has dynamics with differing from IRI

  12. 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

  13. Laboratory diagnosis of pancreatitis and cancer of the pancreas

    International Nuclear Information System (INIS)

    The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsine, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages 3-4) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrinous insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas

  14. 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.

  15. 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.

  16. Significance of C – Peptide in Type 2 Diabetics - A Study in the North Karnataka Population of India

    Directory of Open Access Journals (Sweden)

    Bilal Bin Abdullah

    2010-01-01

    Full Text Available Back ground: Type II DM is a metabolic cum vascular disease and the burden of diabetes is its complications. It is imperative to address the basic biology of diabetes and not to simply treat the symptom complex. Aims and methodology: 1. To estimate the c–peptide levels in elderly diabetics to assess the endogenous insulin secretor function. 2. To know the correlation between obesity and insulin secretion. 3. Modification of treatment in poorly controlled diabetes. The cross sectional study was done in the diabetic outpatient clinic of a tertiary care hospital from Dec 2007 to May 2009. 75 type 2 diabetic patients were evaluated with their fasting plasma glucose, fasting c-peptide levels, HbA1c and BMI. Statistical analysis was done by chi square test and correlation. Results: The fasting c-peptide levels in the obese patients were increased compared to the non obese individuals, indicating insulin resistance. The fasting plasma glucose levels were elevated despite elevated c-peptide levels in the obese patients, proving the role of insulin resistance. The levels of HbA1c were increased more in obese patients indicating poor glycaemic due to insulin resistance. The fasting c-peptide levels decreased as the duration of diabetes increased. Conclusion: The fasting c-peptide levels are useful in type 2 diabetic patients with poor glycaemic control to assess the endogenous insulin reserve and to alter the modality of treatment. Very low c-peptide level indicates need for insulin treatment, and poor prognosis due to poor insulin reserve.

  17. 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...

  18. 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...

  19. 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

    -eight healthy subjects (27 male, 51 female, 43+/-11 years) were subjected to (a). an oral glucose tolerance test and (b). an intravenous injection of 20 pmol GIP/kg body weight, with capillary and venous blood samples collected over 30 min for insulin, C-peptide and GIP (specific immunoassays). Following GIP......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...

  20. 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, ...

  1. 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...

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

    DEFF Research Database (Denmark)

    Kjems, L L; Christiansen, E; Vølund, A; Bergman, R N; Madsbad, Sten

    2000-01-01

    "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity...... from both the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantlydifferent from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 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; Bergman, R N; Madsbad, Sten

    2000-01-01

    "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity...... from both the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantly different from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 0...

  4. Markers of beta cell failure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes

    Science.gov (United States)

    Jones, Angus G; McDonald, Timothy J; Shields, Beverley M; Hill, Anita V; Hyde, Christopher J; Knight, Bridget A; Hattersley, Andrew T

    2016-01-01

    Objective To assess whether clinical characteristics and simple biomarkers of beta cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist therapy in patients with type 2 diabetes. Research Design and Methods We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58mmol/mol (7.5%) commencing GLP-1 receptor agonist therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with beta cell failure and glycemic response (HbA1c change 0 to 6 months, primary outcome) with change in weight (0 to 6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and co-treatment change. Results Reduced glycemic response to GLP-1R agonists was associated with longer duration diabetes, insulin co-treatment, lower fasting C-peptide, lower post meal urine C-peptide creatinine ratio and positive GAD or IA2 islet autoantibodies (p≤0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide ≤0.25nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies: mean HbA1c change -5.2 vs -15.2 mmol/mol (-0.5 vs -1.4%), p=0.005 C-peptide diabetes. PMID:26242184

  5. 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

  6. Variance of the SGK1 gene is associated with insulin secretion in different European populations: results from the TUEF, EUGENE2, and METSIM studies

    DEFF Research Database (Denmark)

    Friedrich, Björn; Weyrich, Peter; Stancáková, Alena; Wang, Jianjung; Kuusisto, Johanna; Laakso, Markku; Sesti, Giorgio; Succurro, Elena; Smith, Ulf; Hansen, Torben; Pedersen, Oluf; Machicao, Fausto; Schäfer, Silke; Lang, Florian; Risler, Teut; Ullrich, Susanne; Stefan, Norbert; Fritsche, Andreas; Häring, Hans-Ulrich

    2008-01-01

    (C-Peptide)/AUC(Glc) ratios (+7.5%, p = 0.04) compared to homozygous wild type TT carriers in the screening population. As interaction analysis for BMIxrs9402571 was significant (p = 0.04) for the endpoint insulin secretion, we stratified the TUEF cohort for BMI, using a cut off point of BMI = 25. The effect on insulin...

  7. 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)

  8. 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.

  9. 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

    transcripts in pancreas, but not in other tissues, 3) the specific immunofluorescence staining of pancreatic islets for human C-peptide, and 4) the synthesis and accumulation of human (pro)insulin in isolated islets. Deletions in the injected DNA fragment of sequences upstream from positions -353, -258, and...

  10. Pancreatic hormones are expressed on the surfaces of human and rat islet cells through exocytotic sites

    DEFF Research Database (Denmark)

    Larsson, L I; Hutton, J C; Madsen, O D;

    1989-01-01

    responsible for the staining. Human insulin cells were surface-labeled by monoclonal antibodies recognizing the mature secretory products, insulin and C-peptide but not with monoclonal antibodies specific for proinsulin. Thus, routing of unprocessed preproinsulin to the cell surface may not account for these...

  11. 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.

  12. 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. 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. Randal (Joshua); S. Vedanta (Sailaja); T.W. Winkle (Thomas); T. Workalemah (Tsegaselassie); I.M. Hei (Iris); V. Steinthorsdotti (Valgerdur); H.M. Stringha (Heather); M.N. Weedo (Michael); E. Wheeler (Eleanor); M.M. Woo (Margaret M.); T. Ferreir (Teresa); R.J. Weyan (Robert); A.V. Segrè (Ayellet); K. Estrad (Karol); J. Luan; J. Nemes (James); J.-H. Par (Ju-Hyun); S. Gustafsson (Stefan); T.O. Kilpeläine (Tuomas); J. Yang (Joanna); N. Bouatia-Naji (Nabila); T. Esko (Tõnu); M.F. Feitosa (Mary Furlan); Z. Kutalik (Zoltán); M. Mangino (Massimo); S. Raychaudhuri (Soumya); R.P. Welch (Ryan); J.H. Zhao; K.K.H. Aben (Katja); D. Absher (Devin); N. Amin (Najaf); A.L. Dixon (Anna); E. Fisher (Eva); N.L. Glazer (Nicole); M.E. Goddard (Michael); N.L. Heard-Costa (Nancy); V. Hoesel (Volker); J.J. Hottenga (Jouke Jan); A. Johansson (Åsa); T. Johnson (Toby); S. Ketkar (Shamika); C. Lamina (Claudia); S. Li (Shengxu); M.F. Moffatt (Miriam); R.H. Myers (Richard); N. Narisu (Narisu); J.R.B. 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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

  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. 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...

  15. Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Knop, Filip K; Lund, Asger; Madsbad, Sten; Holst, Jens Juul; Krarup, Thure; Vilsbøll, Tina

    2014-01-01

    to as one of the most insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance...

  16. 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...

  17. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Krarup, T; Madsbad, S; Holst, Jens Møller

    2002-01-01

    Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose-dependent insulinotropic polypeptide (GIP) is less effective. Our investigation evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C......-peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes....

  18. Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

    Directory of Open Access Journals (Sweden)

    Chazan A.C.S.

    2001-01-01

    Full Text Available To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1, 320 mg gliclazide and bedtime NPH insulin (phase 2, and insulin (phase 3. At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01. Twelve patients (48% reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8 vs 66.7 kg (42.8-101.4 (P<0.05, with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100 increased from 0.9 (0.2-2.1 to 1.3 (0.2-4.7 during combined therapy (P<0.01. Despite a 50% increase in insulin doses in phase 3 (12 U (9-30 vs 18 U (11-60; P<0.01 only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02. A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5 vs 0.6 (0-2.15; P = 0.08 and C-peptide incremental area (2.47 (0.22-6.2 vs 1.2 (0-3.35; P = 0.07 was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response.

  19. Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1.

    Science.gov (United States)

    Chong, Huihui; Yao, Xue; Qiu, Zonglin; Sun, Jianping; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Liu, Shan-Lu; Cui, Sheng; He, Yuxian

    2013-03-01

    Peptides derived from the C-terminal heptad repeat (C peptides) of HIV-1 gp41 are potent inhibitors against virus entry. However, development of a short C peptide possessing high anti-HIV potency is considered a daunting challenge. We recently discovered that the residues Met626 and Thr627 preceding the pocket-binding domain of the C peptide adopt a unique M-T hook structure that is crucial for the design of HIV-1 fusion inhibitors. In this study, we first presented a proof-of-concept prototype that the M-T hook residues can dramatically improve the antiviral activity and thermostability of a short C peptide. We then generated a 24-mer peptide termed MT-SC22EK by incorporating the M-T hook structure to the N terminus of the poorly active short C peptide SC22EK. Amazingly, MT-SC22EK inhibited HIV-1-mediated cell fusion and infection at a level comparable to C34, T1249, SC29EK, and sifuvirtide, and it was highly active against diverse HIV-1 subtypes and variants, including those T20 (enfuvirtide) and SC29EK-resistant viruses. The high-resolution crystal structure of MT-SC22EK reveals the N-terminal M-T hook conformation folded by incorporated Met626 and Thr627 and identifies the C-terminal boundary critical for the anti-HIV activity. Collectively, our studies provide new insights into the mechanisms of HIV-1 fusion and its inhibition. PMID:23233535

  20. Importance of radioimmunoassay of insulin secretion disorder as atherogenic factor

    International Nuclear Information System (INIS)

    Using a radioimmunoassay a C-peptide levei was revealed in children, pregnant and lying-in women as well as in patients with insulin-dependent diabetes mellitus. After breakfast and insulin administration wich curative purposes the IRI concentration in children increased whereas the C-peptide level changed insignificantly. Changes of the insulin secretion were more noticeable in severe diabetes mejlitus with vascular complications and in disease decompensation. The atherogenic nature of the lipid metaboiism (an increase in the cholesterol, triglyceride and β-lipoprotein levels), changes in the liver and tendency to vascular involvement are results of insulin effect inadequacy. Such metabolic derangements in pregnant women create unfavorable conditions for the development of fetus and may lead to early atherogenic processes

  1. 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 of the...... ghrelin levels 150 and 360 min after meal ingestion (p<0.05). The patterns of ghrelin concentrations in the experiments with GLP-1 and placebo administration were inversely related to the respective plasma levels of insulin and C-peptide. CONCLUSIONS: GLP-1 reduces the rise in ghrelin levels in the late...... meal was served. Venous blood was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1 and ghrelin. RESULTS: During the infusion of exogenous GLP-1 and placebo, GLP-1 plasma concentrations reached steady-state levels of 139+/-15 pmol/l and 12+/-2 pmol/l, respectively (p<0...

  2. 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

  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. Assessment of beta-cell function and insulin secretion in subjects that underwent renal transplantation.

    Science.gov (United States)

    Tura, Andrea; Hecking, Manfred; Wolzt, Michael; Saemann, Marcus D; Pacini, Giovanni

    2015-08-01

    In this study we aimed to assess the performance of various indices of beta-cell function derived from oral glucose tolerance test (OGTT) in subjects that underwent renal transplantation. Impaired insulin secretion seems in fact central for development of new onset diabetes after transplantation, but its assessment has not been systematically evaluated. Twenty subjects underwent a 75 g 2h-OGTT for measurement of glucose, insulin, C-peptide. OGTT indices of beta-cell function were either derived by mathematical modeling (yielding the reference index: glucose sensitivity) or were empirical: insulinogenic index (IGI), IGI derived indices, whole shape C-peptide (WHOSH_CP). Indices of beta cell function, showed significant correlation with glucose sensitivity (R(2)=0.40-0.86, all Pbody mass index, mean glycemia. In conclusion, in transplanted subjects OGTT empirical indices are typically acceptable for the estimation of beta-cell function. PMID:26736770

  5. 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...... (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity...... (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were...

  6. 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...

  7. 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)

  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

    .9 mmol X l-1. Glucose turnover was determined by primed constant rate infusion of 3-[3H]glucose. Basal C-peptide (0.46 +/- 0.04 vs. 0.73 +/- 0.06 pmol X ml-1) and glucagon (4 +/- 0.4 vs. 10 +/- 2 pmol X l-1) were lower (P less than 0.05) and epinephrine higher (0.30 +/- 0.06 vs. 0.09 +/- 0.03 nmol X l-1...... 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. 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

  10. 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

  11. 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.

  12. Serum leptin levels in female patients with niddm

    International Nuclear Information System (INIS)

    Objective: To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels. Results: Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P<0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM. Conclusion: Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM. (author)

  13. Association of adiponectin, interleukin (IL)-1ra, inducible protein 10, IL-6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis

    DEFF Research Database (Denmark)

    Pfleger, Claudia Christina; Hansen, Lene; Buschard, K;

    2010-01-01

    The progression of type 1 diabetes after diagnosis is poorly understood. Our aim was to assess the relation of disease progression of juvenile-onset type 1 diabetes, determined by preserved beta cell function the first year after diagnosis, with systemic cytokine concentrations and number of...... autoantibodies. Juvenile patients (n = 227) had a meal-stimulated C-peptide test 1 and 6 months after diagnosis. On the basis of the C-peptide course for the duration of 1-6 months, four progression groups were defined: patients with persistently low beta cell function ('stable-low'), rapid progressers, slow...... patients (P = 0·03 and P = 0·006). IL-1ra, IP-10 and IL-6 did not differ between the groups at any time-point. The number of autoantibodies differed significantly between the groups at 1 month (P = 0·04), where rapid progressers had the largest number. There was no difference between the groups in human...

  14. Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods

    DEFF Research Database (Denmark)

    Kjems, L L; Vølund, A; Madsbad, Sten

    2001-01-01

    AIMS/HYPOTHESIS: We compared four methods to assess their accuracy in measuring insulin secretion during an intravenous glucose tolerance test in patients with Type II (non-insulin-dependent) diabetes mellitus and with varying beta-cell function and matched control subjects. METHODS: Eight control...... subjects and eight Type II diabetic patients underwent an intravenous glucose tolerance test with tolbutamide and an intravenous bolus injection of C-peptide to assess C-peptide kinetics. Insulin secretion rates were determined by the Eaton deconvolution (reference method), the Insulin SECretion method...... first-phase insulin response (r = 0.78). The two-compartment combined model failed to provide reliable estimates of insulin secretion in three of the control subjects and in two patients with Type II diabetes. The four methods were accurate with respect to mean basal and first-phase secretion response...

  15. 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...

  16. Effects of krill oil on endothelial function and other cardiovascular risk factors in participants with type 2 diabetes, a randomized controlled trial

    OpenAIRE

    Lobraico, Jessika M; DiLello, Lauren C; Butler, Amber D; Cordisco, Marie Elena; Petrini, Joann R; Ahmadi, Ramin

    2015-01-01

    Objective The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes. Research design and methods A randomized, double-blind controlled cross-over trial was employed. Outcomes assessed were: endothelial function, blood lipids, glucose, glycated hemoglobin, serum antioxidant level, C peptide, and calculated Homeostatic Model Assessment of...

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

    OpenAIRE

    Abdul Aziz, Siti Hajar; John, Cini Mathew; Mohamed Yusof, Nur Intan Saidaah; Nordin, Massita; Ramasamy, Rajesh; Adam, Aishah; Mohd Fauzi, Fazlin

    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,...

  18. Cotrimoxazole-induced hypoglycemia in an HIV-infected patient

    OpenAIRE

    Hughes, Christine A.; Constance L Chik; Taylor, Geoffrey D

    2001-01-01

    A case of cotrimoxazole-induced hypoglycemia is described in a male patient infected with HIV. Ten days after initiating high dose cotrimoxazole for suspected Pneumocystis carinii pneumonia, the patient developed neuroglycopenic symptoms and diaphoresis. Blood glucose levels were repeatedly low, with elevated insulin and C-peptide levels despite multiple intravenous bolus doses and infusions of dextrose. Hypoglycemia resolved after approximately 36 h of treatment with dextrose and discontinua...

  19. Isolation, Culture, and Imaging of Human Fetal Pancreatic Cell Clusters

    OpenAIRE

    Lopez, Ana D.; Kayali, Ayse G; Hayek, Alberto; King, Charles C.

    2014-01-01

    For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation1-9. However in vitro, genesis of insulin producing cells from human fetal ICCs is low10; results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise...

  20. 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...

  1. 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...

  2. Radioimmunoassay for determination of the hormonal and immune states in patients aczema; psoriasis and neurodermatitis

    International Nuclear Information System (INIS)

    The hormonal and immune status was investigated by a radioimmunoassay in 105 patiets with dermatosis (55 female and 50 male patients aged 15 to 80): 51 suffered frm ecsema, 41 -from psoriasis, and 13 - from neurodermatitis. Serum concentrations of T3, T4, TSH, insulin, trypsin, C-peptide, cortisol, and IgE were investigated. Disorders of the hormonal and immune status were noted in the examinees with relation to sez, type of disease, season, time-period and extent of disease

  3. 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'...

  4. 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...

  5. 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....

  6. 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...

  7. 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.

  8. Mass spectra of proteins and other biomolecules recorded using a handheld instrument

    Science.gov (United States)

    Janfelt, Christian; Talaty, Nari; Mulligan, Christopher C.; Keil, Adam; Ouyang, Zheng; Cooks, R. Graham

    2008-12-01

    Proteins (myoglobin and cytochrome C), peptides (bradykinin and melittin), alkaloids in complex plant materials, and mixtures of phospholipids from a bacterial extract all give characteristic electrospray mass spectra using a handheld tandem mass spectrometer, Mini 10. The mass/charge range of the 10 kg Mini 10 was extended to m/z 2000 using resonant ion ejection at low frequency allowing analysis of proteins with molecular weights up to 17,000 Da. Fragmentation of peptides and proteins was observed.

  9. Type 2 Diabetic Rats on Diet Supplemented With Chromium Malate Show Improved Glycometabolism, Glycometabolism-Related Enzyme Levels and Lipid Metabolism

    OpenAIRE

    Feng, Weiwei; Zhao, Ting; Mao, Guanghua; Wang, Wei; Yun FENG; Li, Fang; Zheng, Daheng; Wu, Huiyu; Jin, Dun; Yang, Liuqing; Wu, Xiangyang

    2015-01-01

    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 effect of chromium malate on glycometabolism, glycometabolism-related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed that fasting blood glucose, serum insulin level, insulin resistance index and C-peptide level in the high dose group had a significant downward trend when compared with the model g...

  10. 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.

  11. Effects of Reducing Sedentary Time on Glucose Metabolism in Pakistani Immigrant Men

    OpenAIRE

    Andersen, Eivind; Ekelund, Ulf; Anderssen, Sigmund A

    2014-01-01

    Purpose: This study aimed to examine the association between changes in objectively measured overall physical activity (PA) and changes in fasting and postprandial plasma insulin, C-peptide, and glucose concentrations in type 2 diabetes-prone immigrant Pakistani men living in Norway and to examine whether this association is explained by changes in moderate and vigorous PA (MVPA) or changes in sedentary time. Methods: The current study is a secondary cohort analysis on data collected ...

  12. Exocrine pancreatic function in diabetes mellitus.

    OpenAIRE

    Dandona, P; Freedman, D B; Foo, Y.; Perkins, J.; Katrak, A; Mikhailidis, D P; Rosalki, S B; Beckett, A. G.

    1984-01-01

    An investigation of serum immunoreactive trypsin concentration and pancreatic isoamylase activity in patients with diabetes mellitus has shown that exocrine pancreatic deficit is maximal in insulin dependent diabetics, intermediate in those controlled with sulphonylureas, and absent in patients controlled with biguanides or diet or both. A significant correlation between the serum concentrations of both these pancreatic enzymes and C peptide was found. Serum pancreatic enzyme concentrations w...

  13. 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...

  14. 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.

  15. 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...

  16. Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma

    OpenAIRE

    Ahn, Chang Ho; Kim, Lee-Kyung; Lee, Jie Eun; Jung, Chan-Hyeon; Min, Se-Hee; Park, Kyong Soo; Kim, Seong Yeon; Cho, Young Min

    2014-01-01

    Background Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas. ...

  17. THYROID FUNCTION AND OTHER METABOLIC CHANGES IN MARRIED AND UNMARRIED FEMALES WITH POLYCYSTIC OVARY SYNDROME

    Directory of Open Access Journals (Sweden)

    Khalaf Ban H

    2011-09-01

    Full Text Available It has been reported that there are significant differences in some biochemical markers of PCOS between married and unmarried women with this disorder. The present study was designed to evaluate the correlation of marital status with thyroid hormones, carbohydrate and lipid metabolism, and androgenic activities. Twenty four married and unmarried women with PCOS were evaluated concerning TSH, T3, T4, glycemic control, C-peptide and lipid profile were evaluated in fasting blood samples. The results showed that in both unmarried and married women with PCOS TSH, FPS, C-peptide, and triglycerides levels were significantly elevated compared to healthy control group. Although serum level of TSH was slightly elevated in married women compared to unmarried group, no significant differences were observed in this respect; the same thing was reported for FPS, serum levels of C-peptide and triglycerides, where those parameters shown to be slightly higher in unmarried women but not significantly different from those reported in married group of PCOS women. In conclusion, no correlations were reported for the marital status with thyroid hormones, carbohydrate and lipid metabolism in Iraqi females with PCOS.

  18. 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

  19. 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.

  20. Diminished hepatic insulin removal in obesity

    International Nuclear Information System (INIS)

    Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out

  1. 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.

  2. Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus

    DEFF Research Database (Denmark)

    Vestergaard, H; Rossen, M; Urhammer, S A;

    1997-01-01

    the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg body weight) in four patients with extreme insulin......-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum...... insulin and C-peptide levels were decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values...

  3. 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

  4. 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

  5. A Nested Case–Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    Science.gov (United States)

    Murphy, Neil; Cross, Amanda J.; Abubakar, Mustapha; Jenab, Mazda; Aleksandrova, Krasimira; Boutron-Ruault, Marie-Christine; Dossus, Laure; Racine, Antoine; Kühn, Tilman; Katzke, Verena A.; Tjønneland, Anne; Petersen, Kristina E. N.; Overvad, Kim; Quirós, J. Ramón; Jakszyn, Paula; Molina-Montes, Esther; Dorronsoro, Miren; Huerta, José-María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Siersema, Peter D.; Peeters, Petra H.; Ohlsson, Bodil; Ericson, Ulrika; Palmqvist, Richard; Nyström, Hanna; Weiderpass, Elisabete; Skeie, Guri; Freisling, Heinz; Kong, So Yeon; Tsilidis, Kostas; Muller, David C.; Riboli, Elio; Gunter, Marc J

    2016-01-01

    Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

    OpenAIRE

    Chazan A.C.S.; Gomes M.B.

    2001-01-01

    To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedti...

  18. 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...

  19. 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...

  20. 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 ...

  1. 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...

  2. 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...

  3. 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.

  4. 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...

  5. Effect of trans-fatty acid intake on insulin sensitivity and intramuscular lipids - a randomized trial in overweight postmenopausal women

    DEFF Research Database (Denmark)

    Bendsen, Nathalie Tommerup; Haugaard, Steen; Larsen, Thomas Meinert;

    2011-01-01

    Intake of industrially produced trans-fatty acids (TFA) has been linked to increased risk of type 2 diabetes mellitus in observational studies. We investigated the causality of this association by examining if a high intake of TFA impairs measures of glucose homeostasis and induces intramuscular...... markers of glucose homeostasis and 4 markers of lipolysis were derived from glucose, insulin, C-peptide, nonesterified fatty acid, and glycerol concentrations during a 3-hour frequent sampling oral glucose tolerance test. Intramuscular lipids were assessed by magnetic resonance spectroscopy. Forty...

  6. Interleukin-1 receptorantagonistbehandling af patienter med type 2-diabetes--sekundaerpublikation

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Faulenbach, Mirjam; Vaag, Allan; Vølund, Aage; Ehses, Jan; Seifert, Burkhardt; Mandrup-Poulsen, Thomas; Donath, Marc

    2007-01-01

    Interleukin-1 receptor antagonist (IL-1Ra) expression is reduced in islets of patients with type 2 diabetes. 70 patients with type 2 diabetes were randomized to treatment with anakinra (IL-1Ra) or placebo for 13 weeks. Following treatment glycated hemoglobin was 0.46 percent lower, C......-peptide secretion was enhanced, and systemic IL-6 and C-reactive protein levels were reduced in the anakinra group compared to the placebo group. Insulin resistance remained unchanged. Blocking IL-1 activity improved glycemia and b-cell secretory function and reduced markers of systemic inflammation. Udgivelsesdato...

  7. 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.

  8. Mekhanizmy narusheniya obmena glyukozy u litss «prediabetom»

    OpenAIRE

    A V Dreval'; I V Misnikova; I V Trigolosova; I A Barsukov

    2009-01-01

    We have performed an estimation of metabolic disorders in 70 persons with various early glucose metabolism abnormalities (IFG and IGT). Oral glucose tolerance test (ОGTT) and intravenous glucose tolerance test (IVGTT) were done in all subjects. HbA1с, insulin and C-peptide levels were also determined. Further НОМА-R, QUICKI, MATSUDA indexes, speed of glucose elimination from the blood (k), production of glucose (H) and a degree of glucose metabolism disorders (pN) were estimated. Glu...

  9. 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...

  10. 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...

  11. 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

    of counterregulatory factors increased during the fast [P Growth hormone secretion increased from the first to third day of fasting (P ...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 ... the fast (P fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value...

  12. 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.

  13. 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...

  14. 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.

  15. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen; Rasmussen, Mette H; Christensen, Mikkel; Knop, Filip Krag

    2010-01-01

    Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from...... dulaglutide reduces plasma glucose, and has an insulinotropic effect increasing insulin and C-peptide levels. Two phase II clinical trials demonstrated a dose-dependent reduction in glycated hemoglobin (HbA1c) of up to 1.52% compared with placebo. Side effects associated with dulaglutide administration were...

  16. 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.

  17. 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

  18. The effect of metformin on blood pressure and metabolism in nondiabetic hypertensive patients

    DEFF Research Database (Denmark)

    Snorgaard, O; Køber, L; Carlsen, J

    1997-01-01

    no impact on the decline in diastolic oBP within this group. Changes in fasting C-peptide and fasting insulin during treatment were unrelated to blood pressure changes. High fasting insulin (> 60 pmol L[-1]) or high fasting C-peptide (> 1000 pmol L[-1]) at baseline did not favour an effect of......OBJECTIVES: To study the effect of metformin on blood pressure and metabolism in nondiabetic hypertensives. DESIGN: A six-week single-blind placebo wash-out, followed by a double-blind placebo-controlled parallel group design with skew randomization (2:2:1) to metformin 850 mg b.i.d. (n = 10......), metformin 500 mg b.i.d. (n = 10), or placebo b.i.d. (n = 5) for 12 weeks. Office blood pressure (oBP), ambulatory blood pressure (aBP), lipoproteins, and oral glucose tolerance (OGTT) were measured/performed before and during treatment. SUBJECTS: Sixteen male and nine female nondiabetic (OGTT) patients...

  19. 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

  20. An Elderly Type 1 Diabetic Patient Presenting with Acute Hyperglycemic Crisis: A Case Report

    Directory of Open Access Journals (Sweden)

    Sedat Gozel

    2014-06-01

    Full Text Available Type 1 diabetes mellitus (T1DM, one of the most common chronic diseases in childhood, is caused by insulin deficiency following destruction of the insulin-producing pancreatic beta cells. One-fourth of cases of T1DM are diagnosed in adults. In elderly patients, T1DM is almost reported only as case reports. It is important to distinguish T1DM from Type 1 diabetes mellitus (T2DM because of the management of two type of diabetes is different. T1DM is suggested by patients who are non-obese, have not any sign of insulin resistance, unresponsive to treatment with oral antidiabetic agents and by the presence of serum autoantibodies against islet cells and low C-peptide levels. We report a case of a 78-year-old female who presented with acute hyperglisemic crisis and was subsequently diagnosed as a case of T1DM with low C-peptide levels and the presence of Anti-GAD65 antibody.

  1. The influence of insulin on the raised plasma fibronectin concentration in human obesity

    DEFF Research Database (Denmark)

    Dejgård, A; Andersen, T; Gluud, C

    1986-01-01

    Plasma concentrations of fibronectin, free insulin, C-peptide and plasma glucose were determined in 40 morbidly obese subjects and in 51 normal weight controls, matched for sex and age. All plasma concentrations were significantly elevated (p less than 0.01) among the obese subjects. A significant...... correlation (r = 0.34, p less than 0.05) between plasma fibronectin and plasma free insulin was found among the obese patients, but not among the controls (r = -0.02, p greater than 0.05). No significant correlation was found between plasma fibronectin and plasma C-peptide, neither in the obese patients nor...... in the controls (obese r = 0.06, controls r = 0.02; p greater than 0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r = 0.21, controls r = 0.15; p greater than 0.05) and percentage overweight (obese r = 0.27, controls r = 0.04; p greater than 0.05). The raised level of...

  2. 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.

  3. 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

  4. 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 (

  5. 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.

  6. 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.)

  7. 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)

  8. 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...

  9. 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

  10. 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...

  11. In Vitro Differentiation of Human Umbilical Cord Blood CD133+Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells

    Science.gov (United States)

    Sahraneshin Samani, Fazel; Ebrahimi, Marzieh; Zandieh, Tahereh; Khoshchehreh, Reyhaneh; Baghaban Eslaminejad, Mohamadreza; Aghdami, Nasser; Baharvand, Hossein

    2015-01-01

    Objective Pancreatic stroma plays an important role in the induction of pancreatic cells by the use of close range signaling. In this respect, we presume that pancreatic mesenchymal cells (PMCs) as a fundamental factor of the stromal niche may have an effective role in differentiation of umbilical cord blood cluster of differentiation 133+ (UCB-CD133+) cells into newly-formed β-cells in vitro. Materials and Methods This study is an experimental research. The UCB-CD133+cells were purified by magnetic activated cell sorting (MACS) and differentiated into insulin producing cells (IPCs) in co-culture, both directly and indirectly with rat PMCs. Immunocytochemistry and enzyme linked immune sorbent assay (ELISA) were used to determine expression and production of insulin and C-peptide at the protein level. Results Our results demonstrated that UCB-CD133+differentiated into IPCs. Cells in islet-like clusters with (out) co-cultured with rat pancreatic stromal cells produced insulin and C-peptide and released them into the culture medium at the end of the induction protocol. However they did not respond well to glucose challenges. Conclusion Rat PMCs possibly affect differentiation of UCB-CD133+cells into IPCs by increasing the number of immature β-cells. PMID:26199900

  12. Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

    Science.gov (United States)

    Polidori, David C; Bergman, Richard N; Chung, Stephanie T; Sumner, Anne E

    2016-06-01

    Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance. PMID:26993071

  13. 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.

  14. In Vitro Differentiation of Human Umbilical Cord Blood CD133+ Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells

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    Fazel Sahraneshin Samani

    2015-07-01

    Full Text Available Objective: Pancreatic stroma plays an important role in the induction of pancreatic cells by the use of close range signaling. In this respect, we presume that pancreatic mesenchymal cells (PMCs as a fundamental factor of the stromal niche may have an effective role in differentiation of umbilical cord blood cluster of differentiation 133+ (UCB-CD133+ cells into newly-formed β-cells in vitro. Materials and Methods: This study is an experimental research. The UCB-CD133+ cells were purified by magnetic activated cell sorting (MACS and differentiated into insulin producing cells (IPCs in co-culture, both directly and indirectly with rat PMCs. Immunocytochemistry and enzyme linked immune sorbent assay (ELISA were used to determine expression and production of insulin and C-peptide at the protein level. Results: Our results demonstrated that UCB-CD133+ differentiated into IPCs. Cells in islet-like clusters with (out co-cultured with rat pancreatic stromal cells produced insulin and C-peptide and released them into the culture medium at the end of the induction protocol. However they did not respond well to glucose challenges. Conclusion: Rat PMCs possibly affect differentiation of UCB-CD133+ cells into IPCs by increasing the number of immature β-cells.

  15. Clinical Characteristics for the Relationship between Type-2 Diabetes Mellitus and Cognitive Impairment: A Cross-Sectional Study.

    Science.gov (United States)

    Zhou, Yi; Fang, Rong; Liu, Li-Hua; Chen, Sheng-Di; Tang, Hui-Dong

    2015-08-01

    We explored the potential differences in cognitive status, lipid and glucose metabolism, ApoEε4 alleles and imaging between diabetic and non-diabetic subjects. 83 subjects with normal cognitive function and 114 mild cognitive impaired patients were divided into four groups by history of diabetes. General demographics was collected from all participants followed by MRI scan, biochemical examinations and a series of neuropsychological tests. Student's t test, multiple regressions and one-way ANOVA were applied to investigate the differences between groups. Comparing diabetic patients with non-diabetic subjects in the mild cognitive impaired group, we found several decreased items in recall of three words in MMSE (p=0.020), AVLT and SCWT (pfasting C-peptide (B= -0.466, p=0.001) had negative effects on the score of MMSE. In addition, diabetic patients treated with insulin and other diabetes medication performed better in part of the AVLT (pcognitive impairment with diabetes mellitus have a worse outcome in attention, information processing speed and memory compared to non-diabetic patients. Higher two-hour glucose level and C-peptide level may be risk factors for severe cognitive impairment in type-2 diabetes mellitus patients. The results of this study also suggest that medication may have effects on cognitive function. PMID:26236545

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

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    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.

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

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    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.

  18. Hypothyroidism Impairs Human Stem Cell-Derived Pancreatic Progenitor Cell Maturation in Mice.

    Science.gov (United States)

    Bruin, Jennifer E; Saber, Nelly; O'Dwyer, Shannon; Fox, Jessica K; Mojibian, Majid; Arora, Payal; Rezania, Alireza; Kieffer, Timothy J

    2016-05-01

    Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study ("chronic") or for 4 weeks posttransplant ("acute"). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon(+) and ghrelin(+) cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation. PMID:26740603

  19. 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

  20. [Functional activity of the liver in immersion and effects of the countermeasures].

    Science.gov (United States)

    Solov'eva, A A; Sedova, E A; Tomilovskaia, E S; Shigueva, T A; Afonin, B V

    2014-01-01

    Two groups of male volunteers for 4-day dry immersion with and w/o countermeasures (support load imitator (SLI) or high-frequency electrostimulator) underwent ultrasonic investigation (USI) of the liver, gastroduodenal organs and vessels, and blood biochemical analysis. Two other groups of volunteers performed the 13C-methacetin breath test (13C-MBT) to study the effects of immersion and SLI on the liver detox activity and metabolic capacity. In immersion, USI diagnosed slowdown of blood flow along the hepatic vein and signs of plethora in the abdominal venous system. In addition, immersion was accompanied by increases in blood pepsinogen, pancreatic amylase, total bilirubin, the "indirect" fraction specifically, insulin and C-peptide. 13C-MBT detected deceleration of 13C-methacetin inactivation and diminution of the liver metabolic capacity. Administration of the countermeasures did not improve the ultrasonic image of hemodynamic alterations in the liver and abdomen significantly. High-frequency electrostimulation cancelled out changes in all biochemical parameters except C-peptide; SLI was favorable to recovery of pepsinogen and amylase baseline values only. Besides, the SLI wearing prevented loss of the 13C-methacetin inactivation rate but was not effective enough against diminution of the hepatic metabolic capacity. PMID:25087407

  1. 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.

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

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    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 

  3. 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.

  4. 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

  5. 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

  6. Sitagliptin is effective and safe as add-on to insulin in patients with absolute insulin deficiency: a case series

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    Kutoh Eiji

    2011-03-01

    Full Text Available Abstract Introduction It is generally believed that incretin-based therapies are effective in patients possessing certain levels of preserved β-cell function. So far, there are no reports that show the effectiveness of dipeptidyl peptidase-4 inhibitors in patients who absolutely lack the capacity for endogenous insulin secretion. Case presentation This report describes the efficacy of sitagliptin in three Japanese patients (a 91-year-old Japanese woman with type 1 diabetes, a 54-year-old Japanese man with type 2 diabetes and a 30-year-old Japanese man with features of both type 1 and type 2 diabetes who had no detectable post-meal C-peptide levels. Although they were receiving intensive insulin therapy together with some oral hypoglycemic agents, their glycemic control remained poor. Sitagliptin was added to the ongoing therapeutic regimen to provide better glycemic control. Although these patients had mild hypoglycemia, effective reductions of hemoglobin A1c levels were observed without any adverse events in the liver and kidney during the following 24 weeks. Two of the patients were able to reduce their insulin doses, and one of the patients could discontinue one of the oral hypoglycemic agents. There was no weight gain or gastrointestinal complaints among the three patients. Post-meal C-peptide levels remained undetectable after sitagliptin treatment. Conclusion This report demonstrates that sitagliptin is effective and safe as an add-on therapy to insulin in reducing blood glucose levels in patients who absolutely lack the capacity for endogenous insulin secretion. The improvement seen in glycemic control could not be due to enhanced endogenous insulin secretion, since post-meal C-peptide levels remained undetectable after sitagliptin treatment, but it could be a result of other factors (for example, suppression of glucagon levels. However, the glucagon-suppressive effect of sitagliptin is known to be rather weak and short-lived. Given this

  7. 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

  8. 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.

  9. 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

  10. The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy.

    Directory of Open Access Journals (Sweden)

    Margrit Urbanek

    Full Text Available BACKGROUND: Since mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome. RESULTS: Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value = 4.4×10(-5, RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1×10(-4, IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3×10(-4, ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value = 1.4×10(-4, LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value = 2.4×10(-4, and IL6 and 1-hour plasma glucose (rs6954897; -2.29 mg/dl decrease per allele G, p-value = 4.3×10(-4. CONCLUSIONS: Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha, may contribute to metabolic phenotypes in pregnant women.

  11. Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: a novel therapy for insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Vanikar, A V; Dave, S D; Thakkar, U G; Trivedi, H L

    2010-01-01

    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 × 10(3)/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 × 10(3)/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. PMID:21197448

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer

    International Nuclear Information System (INIS)

    Background: Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Materials and methods: Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. Results: At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Conclusions: Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk

  16. 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

  17. 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

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

    Science.gov (United States)

    Halschou-Jensen, Kia; Bach Knudsen, Knud E; Nielsen, Søren; Bukhave, Klaus; Andersen, Jens R

    2015-01-01

    In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown l-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing l-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding l-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of l-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % l-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two 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 when l-arabinose was mixed in a solid or semi-solid mixed meal. PMID:25400106

  19. Similar incretin secretion in obese and non-obese Japanese subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Kozawa, Junji; Okita, Kohei; Imagawa, Akihisa; Iwahashi, Hiromi; Holst, Jens Juul; Yamagata, Kazuya; Shimomura, Iichiro

    2010-01-01

    Incretin secretion and effect on insulin secretion are not fully understood in patients with type 2 diabetes. We investigated incretin and insulin secretion after meal intake in obese and non-obese Japanese patients with type 2 diabetes compared to non-diabetic subjects. Nine patients with type 2...... diabetes and 5 non-diabetic subjects were recruited for this study. Five diabetic patients were obese (BMI > or = 25) and 4 patients were non-obese (BMI <25). In response to a mixed meal test, the levels of immunoreactive insulin during 15-90 min and C-peptide during 0-180 min in non-obese patients were...... significantly lower than those in obese patients. Total GLP-1 and active GIP levels showed no significant difference between obese and non-obese patients throughout the meal tolerance test. In addition, there were no significant differences between diabetic patients and non-diabetic subjects. In conclusion...

  20. 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 to...... molecular snapshot of the orchestrated changes in expression of proteins involved in key processes which could be correlated with the altered phenotype of human beta-cells. Collectively our observations prompt research towards the establishment of bioengineered human beta-cells providing a new and needed...... source of cultured human beta-cells for beta-cell research, along with the development of new therapeutic strategies for detection, characterization and treatment of insulinomas....

  1. 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

    : 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......-reactive protein, fibrinogen, and interleukin 6). DESIGN: This was a cross-sectional study of the relations of whole grains, bran, and germ intakes with homocysteine and markers of glycemic control, lipids, and inflammation in 938 healthy men and women. RESULTS: Whole-grain intake was inversely associated...... with homocysteine and markers of glycemic control. Compared with participants in the bottom quintile of whole-grain intake, participants in the highest quintile had 17%, 14%, 14%, and 11% lower concentrations of homocysteine (P

  2. 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...

  3. Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance

    DEFF Research Database (Denmark)

    Breum, Leif; Bjerre, U; Bak, J F;

    1995-01-01

    Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose...... tolerance (IGT) were included in a 12-month, randomized, placebo controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group...... differences (mean +/- SD: F, 10.1 +/- 10.0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose...

  4. 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

    We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty-four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age......: 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...

  5. 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

  6. Peritoneal dialysis in an infant with type 1 diabetes and hyperosmolar coma.

    Science.gov (United States)

    Multari, G; Werner, B; Cervoni, M; Lubrano, R; Costantino, F; Demiraj, V; Pozzilli, P

    2001-02-01

    Hyperosmolar coma which is characterized by severe hyperglycemia in absence of chetosis is very rare in pediatric age with only 11 cases reported in the literature. The outcome of the condition is usually poor with mental retardation being the most common event. Here a case of hyperosmolar coma is described in a female of three months of age who was treated with peritoneal dialysis 11 hours after admittance to hospital. This female patient has been receiving insulin from three months of age and today at the age of 10 years she leads a normal life despite being on insulin therapy. A very low level of C-peptide (<0.3 ng/ml) clearly confirms she is affected by Type 1 diabetes. To our knowledge this is the first case report of hyperosmolar coma in a neonate with Type 1 diabetes who survived this condition without late neurological consequences. PMID:11263466

  7. Association between whole blood mercury and glucose intolerance among adult Inuit in Greenland

    DEFF Research Database (Denmark)

    Jeppesen, Charlotte; Valera, Beatriz; Nielsen, Nina O; Bjerregaard, Peter; Jørgensen, Marit E

    OBJECTIVES: The Arctic diet is partly constituted by traditional food characterized by top predator animals such as whales, walrus, and seals with high mercury content. Mercury exposure has been associated with glucose intolerance in Western populations. We studied the association between whole...... blood mercury and glucose intolerance in a highly exposed non-Western population METHODS: Cross-sectional study of 2640 Inuit (18+ years) with information on ancestry, smoking, waist circumference, total energy intake, and physical activity. Mercury, fasting- and 2-h plasma glucose, insulin, and c......-peptide were measured in blood. Fasting participants without diabetes were classified into normal glucose tolerance, impaired glucose tolerance, impaired fasting glycemia, or type 2 diabetes. We calculated hepatic insulin resistance with homoeostatic model assessment - insulin resistance index, peripheral...

  8. Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Fehse, Frauke; Trautmann, Michael; Holst, Jens Juul;

    2005-01-01

    CONTEXT: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion. OBJECTIVE: The objective of......). Controls included 12 healthy, weight-matched subjects with normal glucose tolerance: nine males, three females; age, 57 +/- 9 yr; and body mass index, 32.0 +/- 3.0 kg/m2. SETTING: The study was conducted at an academic hospital. MAIN OUTCOME MEASURES: Plasma insulin, plasma C-peptide, insulin secretion...... rate (derived by deconvolution), and plasma glucagon were the main outcome measures. RESULTS: DM2 subjects administered saline had diminished first-phase insulin secretion, compared with healthy control subjects. Exenatide-treated DM2 subjects had an insulin secretory pattern similar to healthy...

  9. 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.

  10. 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

  11. Beta-cell dysfunction and low insulin clearance in insulin-resistant human immunodeficiency virus (HIV)-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Vølund, Aage;

    2005-01-01

    OBJECTIVE: To obtain a better understanding of the physiological aspects of glucose homeostasis in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, we evaluated separately beta-cell function and insulin sensitivity after an oral glucose load. DESIGN: Beta-cell function was...... diabetes mellitus or impaired glucose tolerance. Prehepatic insulin secretion rates were estimated by deconvolution of C-peptide concentrations. A composite measure of insulin sensitivity was derived from the OGTT. RESULTS: Beta-cell secretory capacity (i.e. the rate of change in insulin secretion per unit...... change in glucose concentration) was similar in lipodystrophic and nonlipodystrophic patients (6.2 +/- 1.0 mU kg(-1) min(-1) mg(-1) dl vs. 5.4 +/- 0.4, P > 0.4), but insulin sensitivity was reduced by 61% in lipodystrophic patients (P < 0.004). The disposition index (insulin capacity multiplied with...

  12. 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...

  13. Glucose-dependent Insulinotropic Polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul;

    2014-01-01

    CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses of...... glucagon and insulin and glucose disposal in patients with T2DM. DESIGN AND SETTING: We performed a single center, placebo-controlled, cross-over, experimental study. PATIENTS: We studied twelve patients with T2DM (age: 62 ± 1 years [mean ± SEM], body mass index: 29 ± 1 kg/m(2); glycosylated hemoglobin A1c......: 6.5 ± 0.1% [48 ± 2 mmol/mol]). INTERVENTION: We infused physiological amounts of GIP (2 pmol × kg(-1) × min(-1)) or saline. MAIN OUTCOME MEASURES: We measured plasma concentrations of glucagon, glucose, insulin, C-peptide, intact GIP, and amounts of glucose needed to maintain glucose clamps. RESULTS...

  14. 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

    Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease-digested cell DNA effectively detects cross-culture contam...... effective use of gene probes to control the origin of cell cultures.......Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease-digested cell DNA effectively detects cross......-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...

  15. 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

  16. 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

    .0003) compared with placebo. Improvement in glycemic control was evident after 1 week. Body weight decreased by 1.2 kg in the 0.45-mg liraglutide group (P = 0.0184) compared with placebo. The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group (-0.18; P = 0.0244) compared with placebo.......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...

  17. 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

    BACKGROUND: Rye bread has a beneficial effect on the postprandial insulin response in healthy subjects. The role of rye fiber in insulin and glucose metabolism is not known. OBJECTIVE: The aim of the study was to determine the effect of the content of rye fiber in rye breads on postprandial insulin...... high-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......-peptide responses to the rye 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...

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

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    patients suffered from LADA, 3.9% from secondary diabetes, 6.0% from steroid induced diabetes 5.9% had insulinopenic diabetes, whereas 56.7% presented the classic obesity-associated insulin-resistant phenotype. 24.6% was classified as normoinsulinopenic patients. Conclusion: We conclude that newly......Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... 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 < 333 pmol/l and not LADA...

  19. 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

    OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual ß-cell function. RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual ß-cell function (C-peptide positive) and 19...... activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA(1c); time spent with blood glucose <3.9, >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 < 0.001) in C.......1]; P < 0.001). Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide. CONCLUSIONS Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control....

  20. Insulin secretion in lipodystrophic HIV-infected patients is associated with high levels of nonglucose secretagogues and insulin resistance of beta-cells

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Storgaard, Heidi;

    2004-01-01

    We examined whether plasma concentrations of nonglucose insulin secretagogues are associated with prehepatic insulin secretion rates (ISR) in nondiabetic, insulin-resistant, human immunodeficiency virus (HIV)-infected, lipodystrophic patients (LIPO). Additionally, the negative feedback of insulin...... on ISR was evaluated. ISR were estimated by deconvolution of plasma C-peptide concentrations during fasting (basal) and during the last 30 min of a 120-min euglycemic insulin clamp (40 mU.m(-2).min(-1)). Eighteen normoglycemic LIPO were compared with 25 normoglycemic HIV-infected patients without...... lipodystrophy (controls). Thirty minutes before start of the clamp, a bolus of glucose was injected intravenously to stimulate endogenous insulin secretion. Insulin sensitivity index (SiRd) was estimated from glucose tracer analysis. LIPO displayed increased basal ISR (69%), clamp ISR (114%), basal insulin (130...

  1. 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.; Vogel, Ulla Birgitte; Møller, P.; Lindecrona, R.; Wallin, H.; Poulsen, H. E.; Loft, S.; Dragsted, L. O.

    2008-01-01

    proliferation were determined in colon, and a metabonomic analysis was performed in plasma and urine. The sugars increased the mutation rates in colon and the bulky adduct levels in colon and liver to a similar extent. All sugars decrease the caecal concentration of acetic acid and propionic acid. The......% 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 and...... metabonomic studies indicated disturbed amino acid metabolism and decrease in plasma and urinary acetate as a common feature for all sugars and confirmed triglyceridemic effects of fructose. In conclusion, the genotoxicity may be related to the altered chemical environment in the caecum and thereby also in...

  2. Status of incretion function of pancreas ant their reserve possibilities in delayed terms after irradiation by low doses

    International Nuclear Information System (INIS)

    By radio-immune method the contents of both the insulin and C-peptide in Chernobyl accident liquidators' blood serum on empty stomach and after two hours of glucose loading are examined. Concentration of the hormone and its by-product were analyzed in dependence from year of participation in liquidation, exposition duration, dose of external irradiation, rate of radiation contamination of zone and liquidators' age. At that mean values were compared with indexes of control group and frequency of normal and changed concentration of these indexes were studied. It is revealed, that largest differences between initial and post-loading insulin content have liquidators: - participated in accident works in 1986 (2.13 times); - with exposition duration from 2 up to 6 month (2.2 times); - with absorbed doses 0.51-1.0 Gy

  3. 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.

  4. 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...

  5. 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.

  6. Rapid Normalization of High Glutamic Acid Decarboxylase Autoantibody Titers and Preserved Endogenous Insulin Secretion in a Patient with Diabetes Mellitus: A Case Report and Literature Review.

    Science.gov (United States)

    Ohara, Nobumasa; Kaneko, Masanori; Furukawa, Tatsuo; Koike, Tadashi; Sone, Hirohito; Tanaka, Shoichiro; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 59-year-old Japanese woman developed diabetes mellitus without ketoacidosis in the presence of glutamic acid decarboxylase autoantibody (GADA) (24.7 U/mL). After the amelioration of her hyperglycemia, the patient had a relatively preserved serum C-peptide level. Her endogenous insulin secretion capacity remained almost unchanged during 5 years of insulin therapy. The patient's GADA titers normalized within 15 months. The islet-related autoantibodies, including GADA, are believed to be produced following the autoimmune destruction of pancreatic beta cells and are predictive markers of type 1 diabetes mellitus. Therefore, the transient appearance of GADA in our patient may have reflected pancreatic autoimmune processes that terminated without progression to insulin deficiency. PMID:26935368

  7. Fulminant Type 1 Diabetes Mellitus Associated with Coxsackie Virus Type A2 Infection: A Case Report and Literature Review.

    Science.gov (United States)

    Ohara, Nobumasa; Kaneko, Masanori; Nishibori, Takeaki; Sato, Kazuhiro; Furukawa, Tatsuo; Koike, Tadashi; Sone, Hirohito; Kaneko, Kenzo; Kamoi, Kyuzi

    2016-01-01

    A 65-year-old Japanese man presented to our hospital in June 2013 with a 6-day history of fever and fatigue, a 24-h history of thirst, and polyuria. His temperature was 37.8°C and he was alert. However, laboratory tests revealed severe hyperglycemia, undetectable C-peptide levels, and diabetic ketoacidosis. Serum antibody testing confirmed a Coxsackie virus A2 infection. A variety of viral infections are reported to be involved in the development of fulminant type 1 diabetes mellitus (FT1D). Our patient is the first reported case of FT1D associated with Coxsackie virus A2 infection and supports the etiological role of common viral infections in FT1D. PMID:26984083

  8. Metabolic and clinical effects of Ramadan fasting in patients with type II diabetes

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes. Results: Daily cholesterol intake increased in all subjects (p 0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p < 0.05), C-peptide (p < 0.01) and insulin resistance (p < 0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study. Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavorably altered due to changes in both diet and biochemical response to starvation. (author)

  9. In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R; Andersen, Ulrik B; Vølund, Aage; Iversen, Johan; Nielsen, Jens Ole; Madsbad, Sten

    2005-01-01

    , human immunodeficiency virus (HIV)-infected patients with and without lipodystrophy. We studied 18 HIV-infected patients with lipodystrophy (LIPO) on antiretroviral therapy and 25 HIV-infected patients without lipodystrophy (controls) of whom 18 were on antiretroviral therapy and 7 were not. Posthepatic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P < .001), impaired insulin sensitivity index (M value, -29%, P < .001), and reduced MCRi (-17%, P < .01). Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P < .02 and r...

  10. 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......, the secretion patterns of SP and IP of 16 HIV-infected men with lipodystrophy (LIPO) and 15 HIV-infected men without lipodystrophy (NONLIPO) were studied during an oral glucose tolerance test (OGTT). All patients received highly active antiretroviral therapy. Insulin secretion rates were determined by...... deconvolution of plasma C-peptide concentrations. More LIPO than NONLIPO patients displayed diabetes mellitus and impaired glucose tolerance than normal glucose tolerance (LIPO 2/8/6 vs NONLIPO 1/2/12, P = .05). LIPO patients had increased fasting levels of SP and IP, ratio of SP/IP, and area under the curve of...

  11. 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

  12. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers

    DEFF Research Database (Denmark)

    Nauck, Michael A; Heimesaat, Markus M; Behle, Kai; Holst, Jens Juul; Nauck, Markus S; Ritzel, Robert; Hüfner, Michael; Schmiegel, Wolff H

    2002-01-01

    neuroglucopenic symptoms were assessed, and cognitive function was tested at each plateau. Insulin secretion rates were estimated by deconvolution (two-compartment model of C-peptide kinetics). At insulin concentrations of approximately 45 mU/liter, glucose infusion rates were similar with and without GLP-1 (P...... other counterregulatory hormones and autonomic or neuroglucopenic symptom scores increased, and cognitive functions decreased with decreasing glucose concentrations, but there were no significant differences comparing experiments with GLP-1 or placebo, except for a significant reduction of GH responses...... with normal oral glucose tolerance received infusions of regular insulin (1 mU x kg(-1) x min(-1)) over 360 min on two occasions in the fasting state. Capillary glucose concentrations were clamped at plateaus of 4.3, 3.7, 3.0, and 2.3 mmol/liter for 90 min each (stepwise hypoglycemic clamp); on one...

  13. Monitoring of celiac plexus block in chronic pancreatitis

    DEFF Research Database (Denmark)

    Myhre, John Gabriel; Hilsted, J; Tronier, B;

    1989-01-01

    Pharmacological, percutaneous celiac plexus blockade is often inefficient in the treatment of pain in chronic pancreatitis. Lack of efficiency could be due to incomplete denervation of the plexus; however, a method for measuring the completeness of celiac plexus blockade is not yet available. We...... block in 6 patients with chronic pancreatitis. Blood pressure decreased and heart rate increased after the block (P less than 0.025), whereas no significant change was found in hepato-splanchnic vascular resistance nor in the change of these parameters during transition from the supine to standing...... position. Pancreatic hormones (C-peptide, free insulin, glucagon, pancreatic polypeptide and somatostatin) did not change in response to standing, either before or after the block. The cardiovascular variables were normalized the day after the block, and all the patients were in their habitual state...

  14. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan;

    2007-01-01

    proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive......BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...... (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels...

  15. Resistant starch and arabinoxylan augment SCFA absorption, but affect postprandial glucose and insulin responses differently - CORRIGENDUM

    DEFF Research Database (Denmark)

    Ingerslev, Anne Krog; Theil, Peter Kappel; Hedemann, Mette Skou;

    2015-01-01

    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 < 0.01) in AXD, RSD, and WSD fed pigs, respectively, with the largest relative increase for butyrate in response to arabinoxylan supplementation. In......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...... conclusion, RSD and AXD had different effects on net portal insulin and glucose flux, suggesting different impact of arabinoxylan and resistant starch on human health....

  16. Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Cavelti-Weder, Claudia; Babians-Brunner, Andrea; Keller, Cornelia; Stahel, Marc A; Kurz-Levin, Malaika; Zayed, Hany; Solinger, Alan M; Mandrup-Poulsen, Thomas; Dinarello, Charles A; Donath, Marc Y

    2012-01-01

    OBJECTIVEMetabolic activation of the innate immune system governed by interleukin (IL)-1ß contributes to ß-cell failure in type 2 diabetes. Gevokizumab is a novel, human-engineered monoclonal anti-IL-1ß antibody. We evaluated the safety and biological activity of gevokizumab in patients with type 2...... diabetes.RESEARCH DESIGN AND METHODSIn a placebo-controlled, dose-escalation study, a total of 98 patients were randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules. The primary objective of the study was to evaluate the safety profile of.......85% after 1, 2 (P = 0.017), and 3 (P = 0.049) months, respectively, along with enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines.CONCLUSIONSThis novel IL-1ß-neutralizing antibody improved glycemia, possibly via restored...

  17. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

    Gyldenløve, Mette; Storgaard, Heidi; Holst, Jens Juul;

    2015-01-01

    differences between groups in plasma glucose, insulin, C-peptide, and glucagon during the clamp. LIMITATIONS: The classic hyperinsulinemic euglycemic clamp technique does not allow assessment of endogenous glucose production. CONCLUSION: Patients with psoriasis were more insulin resistant compared with...... have used suboptimal methodology. The hyperinsulinemic euglycemic clamp remains the gold standard for quantifying whole-body insulin sensitivity. OBJECTIVE: We sought to investigate if normal glucose-tolerant patients with psoriasis exhibit impaired insulin sensitivity. METHODS: Three......-hour hyperinsulinemic euglycemic clamps were performed in 16 patients with moderate to severe, untreated psoriasis and 16 matched control subjects. RESULTS: The 2 groups were similar with regard to age, gender, body mass index, body composition, physical activity, fasting plasma glucose, and glycosylated hemoglobin...

  18. Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Meier, Juris J; Weyhe, Dirk; Michaely, Mark;

    2004-01-01

    GLP-1 (1.2 pmol x kg x min) and placebo over 8 hrs, each administered in randomized order in the fasting state. C-reactive protein concentrations of 4.9+/-4.2 mg/dL indicated a systemic inflammation. Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon, and......OBJECTIVE: Hyperglycemia is a major risk factor for a poor outcome after major surgery in patients with type 2 diabetes. Intensive insulin treatment aiming at normoglycemia can markedly improve the survival of critically ill patients, but the broad clinical application is limited by its...... practicability and the risk of hypoglycemia. Therefore, the glucose-lowering effect of the incretin hormone glucagon-like peptide 1 (GLP-1) was investigated in patients with type 2 diabetes after major surgery. DESIGN: Randomised clinical study. SETTING: A surgical unit of a university hospital. PATIENTS AND...

  19. Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis

    DEFF Research Database (Denmark)

    Larsen, S; Hilsted, J; Tronier, B;

    1987-01-01

    Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B...... less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in...... insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of...

  20. 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

  1. New definition for the partial remission period in children and adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Mortensen, Henrik B; Hougaard, Philip; Swift, Peter; Hansen, Lars; Holl, Reinhard W; Hoey, Hilary; Bjoerndalen, Hilde; de Beaufort, Carine; Chiarelli, Francesco; Danne, Thomas; Schoenle, Eugen J; Aman, Jan

    2009-01-01

    -peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.......OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months...... the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess "enterogastrone" activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 +/- 3.3 yr, body mass....... 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 31 +/- 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively (P Gastric half-emptying times were 120 +/- 9 and 120 +/- 18 min (P = 1...

  3. 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

  4. 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...

  5. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects

    DEFF Research Database (Denmark)

    Meier, Juris J; Kemmeries, Guido; Holst, Jens Juul;

    2005-01-01

    Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore......, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 +/- 4 years, BMI 25.0 +/- 4.9 kg/m2) were studied with an infusion of GLP-1 (0.8 pmol.kg(-1).min(-1) from -30 to 240 min) or placebo......) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution...

  6. 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

  7. Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects

    DEFF Research Database (Denmark)

    Meier, Juris J; Nauck, Michael A; Kranz, Daniel; Holst, Jens J; Deacon, Carolyn F; Gaeckler, Dirk; Schmidt, Wolfgang E; Gallwitz, Baptist

    2004-01-01

    Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important factors in the pathogenesis of type 2 diabetes and have a promising therapeutic potential. Alterations of their secretion, in vivo degradation, and elimination in patients with chronic renal insufficiency (CRI......, C-peptide, GLP-1 (total and intact), and GIP (total and intact; specific immunoassays). Plasma levels of GIP (3-42) and GLP-1 (9-36 amide) were calculated. Statistics were performed using repeated-measures and one-way ANOVA. After the oral glucose load, plasma concentrations of intact GLP-1 and...... elimination of GIP and GLP-1. The initial dipeptidyl peptidase IV-mediated degradation of both hormones is almost unaffected by impairments in renal function. Delayed elimination of GLP-1 and GIP in renal insufficiency may influence the pharmacokinetics and pharmacodynamics of dipeptidyl peptidase IV...

  8. Removal of Duodenum Elicits GLP-1 Secretion

    DEFF Research Database (Denmark)

    Muscogiuri, Giovanna; Mezza, Teresa; Prioletta, Annamaria;

    2013-01-01

    ) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase...... in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R(2) = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R(2) = 0.46; P = 0.03) and C-peptide (R(2) = 0.37; P = 0.04). Given that the...... and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion....

  9. Metabolism and pharmacokinetic of cyclo-peptides and peptides. Use of radioelement and stable isotopes; Metabolisme et pharmacocinetique de composes peptidiques et cyclopeptidiques: utilisation de radioelements et d'isotopes stables

    Energy Technology Data Exchange (ETDEWEB)

    Aninat, C.

    2003-10-15

    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 ({sup 13}C, {sup 15}N, and {sup 13}C/{sup 15}N) or radioactive ({sup 14}C) 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. 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)

    2003-01-01

    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...

  11. Normal blood pressure and preserved diurnal variation in offspring of type 2 diabetic patients characterized by features of the metabolic syndrome: the Fredericia Study

    DEFF Research Database (Denmark)

    Foss, Catherine Hauerslev; Vestbo, Else; Frøland, Anders; Gjessing, Hans; Mogensen, Carl Erik; Damsgaard, Else Marie Skjøde

    . CONCLUSIONS: This study shows a preserved diurnal BP profile and a normal BP level in the nondiabetic glucose-tolerant offspring of type 2 diabetic subjects compared with the offspring of nondiabetic subjects, although the offspring of diabetic patients are characterized by features of the metabolic syndrome.......OBJECTIVE: To examine whether an elevated blood pressure (BP) level and an impaired reduction in nocturnal BP are already present in nondiabetic first-degree relatives of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We examined 253 offspring of type 2 diabetic patients using ambulatory BP...... between the nondiabetic glucose-tolerant offspring of type 2 diabetic subjects and the offspring of nondiabetic subjects. BMI (P < 0.05 and P < 0.01, male vs. female), waist-to-hip ratio (P < 0.05), fasting blood glucose (P < 0.01), C-peptide (P < 0.05 and P < 0.01, male vs. female), insulin resistance...

  12. Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose- and non-glucose-induced insulin secretion in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Aaboe, Kasper; Knop, Filip Krag; Vilsbøll, Tina; Deacon, Carolyn F.; Holst, Jens Juul; Madsbad, Sten; Krarup, Thure

    2010-01-01

    AIM: To examine the effects of 12 weeks of treatment with the DPP-4 inhibitor, sitagliptin, on gastrointestinal hormone responses to a standardized mixed meal and beta cell secretory capacity, measured as glucose and non-glucose induced insulin secretion during a hyperglycaemic clamp, in patients...... with type 2 diabetes. METHOD: A double-blinded, placebo-controlled study over 12 weeks in which 24 patients with T2DM were randomized to receive either sitagliptin (Januvia) 100 mg qd or placebo as an add-on therapy to metformin. In week 0, 1 and 12 patients underwent a meal test and a 90-min 20 m......M hyperglycaemic clamp with 5 g of l-arginine infusion. Main outcome measure was postprandial total glucagon-like peptide 1 (GLP-1) concentration. Additional measures were insulin and C-peptide, glycaemic control, intact and total peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP), and intact...

  13. Effects of saxagliptin on β-cell stimulation and insulin secretion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Henry, R R; Smith, Susanne; Schwartz, Saul; Mudaliar, S R; Deacon, C F; Holst, Jens Juul; Duan, R Y; Chen, R S; List, J F

    2011-01-01

    Aim: To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on ß-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes. Methods: Patients in this randomized, parallel-group, double-blind, placebo......-controlled study were drug-naÏve, aged 43–69 years, with baseline haemoglobin A1c (HbA1c) 5.9–8.1%. Twenty patients received saxagliptin 5 mg once daily; 16 received placebo. Patients were assessed at baseline and week 12 by intravenous hyperglycaemic clamp (0–180 min, fasting state), and intravenous......-oral hyperglycaemic clamp (180–480 min, postprandial state) following oral ingestion of 75 g glucose. Primary and secondary endpoints were percent changes from baseline in insulin secretion during postprandial and fasting states, respectively. Insulin secretion was calculated by C-peptide deconvolution. Results...

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. A New Method for Local Dependence Map and Its Applications

    Directory of Open Access Journals (Sweden)

    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

  19. Does diabetes appear in distinct phenotypes in young people? Results of the diabetes mellitus incidence Cohort Registry (DiMelli.

    Directory of Open Access Journals (Sweden)

    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

  20. Screening of soy protein-derived hypotriglyceridemic di-peptides in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    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.

  1. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation.

    Directory of Open Access Journals (Sweden)

    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

  2. Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study

    Directory of Open Access Journals (Sweden)

    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.

  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. 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)

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Lupus anti-ribosomal P autoantibody proteomes express convergent biclonal signatures.

    Science.gov (United States)

    Al Kindi, M A; Colella, A D; Beroukas, D; Chataway, T K; Gordon, T P

    2016-04-01

    Lupus-specific anti-ribosomal P (anti-Rib-P) autoantibodies have been implicated in the pathogenesis of neurological complications in systemic lupus erythematosus (SLE). The aim of the present study was to determine variable (V)-region signatures of secreted autoantibody proteomes specific for the Rib-P heterocomplex and investigate the molecular basis of the reported cross-reactivity with Sm autoantigen. Anti-Rib-P immunoglobulins (IgGs) were purified from six anti-Rib-P-positive sera by elution from enzyme-linked immunosorbent assay (ELISA) plates coated with either native Rib-P proteins or an 11-amino acid peptide (11-C peptide) representing the conserved COOH-terminal P epitope. Rib-P- and 11-C peptide-specific IgGs were analysed for heavy (H) and light (L) chain clonality and V-region expression using an electrophoretic and de-novo and database-driven mass spectrometric sequencing workflow. Purified anti-Rib-P and anti-SmD IgGs were tested for cross-reactivity on ELISA and their proteome data sets analysed for shared clonotypes. Anti-Rib-P autoantibody proteomes were IgG1 kappa-restricted and comprised two public clonotypes defined by unique H/L chain pairings. The major clonotypic population was specific for the common COOH-terminal epitope, while the second shared the same pairing signature as a recently reported anti-SmD clonotype, accounting for two-way immunoassay cross-reactivity between these lupus autoantibodies. Sequence convergence of anti-Rib-P proteomes suggests common molecular pathways of autoantibody production and identifies stereotyped clonal populations that are thought to play a pathogenic role in neuropsychiatric lupus. Shared clonotypic structures for anti-Rib-P and anti-Sm responses suggest a common B cell clonal origin for subsets of these lupus-specific autoantibodies. PMID:26646815

  10. Computational design of peptide-Au cluster probe for sensitive detection of αIIbβ3 integrin

    Science.gov (United States)

    Zhao, Lina; Zhai, Jiao; Zhang, Xuejie; Gao, Xueyun; Fang, Xiaohong; Li, Jingyuan

    2016-02-01

    We have designed a novel peptide-Au cluster probe to specifically bind to αIIbβ3 integrin. As indicated by molecular dynamics (MD) simulations, the binding mode of the native ligand of αIIbβ3 integrin, γC peptide, can be realized by the designed probe. More importantly, the peptide-Au probe can provide multiple coating peptides to form additional salt bridges with protein, and the binding stability of the probe is comparable to the native ligand. The designed probe was then successfully synthesized. The specific binding in a cellular environment was validated by colocalization analysis of confocal microscopy. In addition, the binding affinity was confirmed by atomic force microscopy (AFM) based single molecule force spectroscopy. Our results suggest the combination of computational design and experimental verification can be a useful strategy for the development of nanoprobes.We have designed a novel peptide-Au cluster probe to specifically bind to αIIbβ3 integrin. As indicated by molecular dynamics (MD) simulations, the binding mode of the native ligand of αIIbβ3 integrin, γC peptide, can be realized by the designed probe. More importantly, the peptide-Au probe can provide multiple coating peptides to form additional salt bridges with protein, and the binding stability of the probe is comparable to the native ligand. The designed probe was then successfully synthesized. The specific binding in a cellular environment was validated by colocalization analysis of confocal microscopy. In addition, the binding affinity was confirmed by atomic force microscopy (AFM) based single molecule force spectroscopy. Our results suggest the combination of computational design and experimental verification can be a useful strategy for the development of nanoprobes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09175f

  11. Directed differentiation of rhesus monkey ES cells into pancreatic cell phenotypes

    Directory of Open Access Journals (Sweden)

    Nauert Brian

    2004-06-01

    Full Text Available Abstract Embryonic stem cells (ES can self-replicate and differentiate into all cell types including insulin-producing, beta-like cells and could, therefore, be used to treat diabetes mellitus. To date, results of stem cell differentiation into beta cells have been debated, largely due to difficulties in defining the identity of a beta cell. We have recently differentiated non-human primate (rhesus embryonic stem (rES cell lines into insulin producing, beta-like cells with the beta cell growth factor, Exendin-4 and using C-peptide as a phenotype marker. Cell development was characterized at each stage by gene and protein expression. Insulin, NKX6.1 and glucagon mRNA were expressed in stage 4 cells but not in early undifferentiated cells. We concluded that rES cells could be differentiated ex vivo to insulin producing cells. These differentiated rES cells could be used to develop a non-human primate model for evaluating cell therapy to treat diabetes. To facilitate the identification of beta-like cells and to track the cells post-transplantation, we have developed a marker gene construct: fusing the human insulin promoter (HIP to the green fluorescent protein (GFP gene. This construct was transfected into stage 3 rES derived cells and subsequent GFP expression was identified in C-peptide positive cells, thereby substantiating endogenous insulin production by rES derived cells. Using this GFP detection system, we will enrich our population of insulin producing rES derived cells and track these cells post-transplantation in the non-human primate model.

  12. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

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    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.

  13. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

    Directory of Open Access Journals (Sweden)

    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.

  14. In Vivo Assessment of Antioxidants and Antihyperglycemic Effect of Barleria cristata leaves in Streptozotocin- Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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

  17. Effects of prolonged exposure to hypobaric hypoxia on oxidative stress, inflammation and gluco-insular regulation: the not-so-sweet price for good regulation.

    Directory of Open Access Journals (Sweden)

    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.

  18. Characteristics and Determinants of Partial Remission in Children with Type 1 Diabetes Using the Insulin-Dose-Adjusted A1C Definition

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    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.

  19. 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.

  20. Practical Classification Guidelines for Diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis

    Science.gov (United States)

    Hope, Suzy V; Wienand-Barnett, Sophie; Shepherd, Maggie; King, Sophie M; Fox, Charles; Khunti, Kamlesh; Oram, Richard A; Knight, Bea A; Hattersley, Andrew T; Jones, Angus G; Shields, Beverley M

    2016-01-01

    Background Differentiating between type 1 and type 2 diabetes is fundamental to ensuring appropriate management of patients, but can be challenging, especially when treating with insulin. The 2010 UK Practical Classification Guidelines for Diabetes were developed to help make the differentiation. Aim To assess diagnostic accuracy of the UK guidelines against ‘gold standard’ definitions of type 1 and type 2 diabetes based on measured C-peptide levels. Design and setting In total, 601 adults with insulin-treated diabetes and diabetes duration ≥5 years were recruited in Devon, Northamptonshire, and Leicestershire. Method Baseline information and home urine sample were collected. Urinary C-peptide creatinine ratio (UCPCR) measures endogenous insulin production. Gold standard type 1 diabetes was defined as continuous insulin treatment within 3 years of diagnosis and absolute insulin deficiency (UCPCR<0.2 nmol/mmol ≥5 years post-diagnosis); all others classed as having type 2 diabetes. Diagnostic performance of the clinical criteria was assessed and other criteria explored using receiver operating characteristic (ROC) curves. Results UK guidelines correctly classified 86% of participants. Most misclassifications occurred in patients classed as having type 1 diabetes who had significant endogenous insulin levels (57 out of 601; 9%); most in those diagnosed ≥35 years and treated with insulin from diagnosis, where 37 out of 66 (56%) were misclassified. Time to insulin and age at diagnosis performed best in predicting long-term endogenous insulin production (ROC AUC = 0.904 and 0.871); BMI was a less strong predictor of diabetes type (AUC = 0.824). Conclusion Current UK guidelines provide a pragmatic clinical approach to classification reflecting long-term endogenous insulin production; caution is needed in older patients commencing insulin from diagnosis, where misclassification rates are increased. PMID:27080317

  1. 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.

  2. 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

  3. 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.

  4. Classificação do diabete melito Diabetes mellitus classification

    Directory of Open Access Journals (Sweden)

    Jorge de Faria Maraschin

    2010-08-01

    Full Text Available A correta classificação do diabete melito (DM permite o tratamento mais adequado e compreende quatro categorias: DM tipo 1; DM tipo 2; Outros tipos e Diabete Gestacional. Em alguns casos, pode ocorrer sobreposição de quadros, principalmente no DM que inicia no adulto jovem ou que se apresenta inicialmente com cetoacidose, intermediários ao DM 1 e DM 2. Assim, acréscimos ao sistema de classificação clássico têm sido propostos, avaliando a presença de autoimunidade (anticorpos e a função de célula β (peptídeo-C para definir mais precisamente os subtipos. O objetivo desta revisão foi de analisar o desempenho desses índices diagnósticos para a classificação do DM e descrever os subtipos em detalhe. Os anticorpos contra o pâncreas evidenciam a autoimunidade, sendo o anticorpo contra insulina o mais acurado antes dos 5 anos de idade e o anti-descarboxilase do ácido glutâmico para início da doença acima dos 20 anos, é esse o teste que permanece positivo por mais tempo. Já a medida do peptídeo-C avalia a reserva pancreática de insulina, e os métodos de estímulo mais usados são a medida após refeição ou após glucagon endovenoso. Valores de peptídeo-C The right classification for diabetes mellitus (DM allows a more adequate treatment and comprises four categories: type 1 DM, type 2 DM, other types, and gestational diabetes. In some cases, there might be a superposition of situations, especially with regard to the DM that initiates in the young adult or is initially presented with diabetic ketoacidosis intermediately to type 1 and 2 DM. Thus, additions to the classic classification system have been proposed as assessing the presence of autoimmunity (antibody and b cell function (C-peptide to precisely define the subtypes. The aim of this literature review was to analyze these diagnostic indexes’ performance in the DM classification and to describe subtypes with details. The antibodies against pancreas confirm

  5. 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

  6. 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

  7. 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

  8. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

    1999-01-01

    OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...... under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration, whereas glucagon levels were unchanged. Neither triglycerides nor free fatty acids were affected. GLP-1 administration decreased hunger and prospective food intake and increased satiety, whereas...

  18. Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients.

    Science.gov (United States)

    Toma, Andréa; Haddouk, Samy; Briand, Jean-Paul; Camoin, Luc; Gahery, Hanne; Connan, Francine; Dubois-Laforgue, Danielle; Caillat-Zucman, Sophie; Guillet, Jean-Gérard; Carel, Jean-Claude; Muller, Sylviane; Choppin, Jeannine; Boitard, Christian

    2005-07-26

    Proinsulin is a key autoantigen in type 1 diabetes. Evidence in the mouse has underscored the importance of the insulin B chain region in autoimmunity to pancreatic beta cells. In man, a majority of proteasome cleavage sites are predicted by proteasome cleavage algorithms within this region. To study CD8+ T cell responses to the insulin B chain and adjacent C peptide, we selected 8- to 11-mer peptides according to proteasome cleavage patterns obtained by digestion of two peptides covering proinsulin residues 28 to 64. We studied their binding to purified HLA class I molecules and their recognition by T cells from diabetic patients. Peripheral blood mononuclear cells from 17 of 19 recent-onset and 12 of 13 long-standing type 1 diabetic patients produced IFN-gamma in response to proinsulin peptides as shown by using an ELISPOT assay. In most patients, the response was against several class I-restricted peptides. Nine peptides were recognized within the proinsulin region covering residues 34 to 61. Four yielded a high frequency of recognition in HLA-A1 and -B8 patients. Three peptides located in the proinsulin region 41-51 were shown to bind several HLA molecules and to be recognized in a high percentage of diabetic patients. PMID:16030147

  19. Congenital hyperinsulinism in Ukraine

    DEFF Research Database (Denmark)

    Globa, E.; Zelinska, N.; Flanagan, S.;

    2015-01-01

    was undertaken for seven patients with CHI from 9 families. KCNJ11, ABCC8, HNF4A genes were sequenced in all patients. For those who were negative in the initial screening, were also tested for GLUD1 gene, as well as tNGS of all known CHI genes was performed. 18F-DOPA PET-CT (and 68Ga-DOTA PET......-CT) scans were performed in selected cases. Results: In seven patients hypoglycaemia (glucose 0,8 [0,5; 1,2] mmol/l) with detectable insulin (43,1 [1,2; 45,9] mIU/l) and/or C-peptide (6,9 [1,1; 9,9] ng/ml) confirmed CHI. The median age at diagnosis was 55,4 [1,0; 330] days and the median birth weight was...... 4078 [2850; 5200] g. The incidence of CHI in the Ukraine was calculated at 1 in 258,650 births. Mutations were detected in 6/7 patients. In one patient without a mutation, 18F-DOPA and 68Ga-DOTA PET-CT scanning revealed diffuse disease. All patients showed a poor response to medication and had varying...

  20. 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.

  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. 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

  3. 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.

  4. Carriers of the TCF7L2 rs7903146 TT genotype have elevated levels of plasma glucose, serum proinsulin and plasma gastric inhibitory polypeptide (GIP) during a meal test

    DEFF Research Database (Denmark)

    Gjesing, A P; Kjems, L L; Vestmar, M A;

    2011-01-01

    glucose-tolerant men (age 54¿±¿7 years and BMI 26¿±¿3 kg/m2) with rs7903146 TT genotype and 31 glucose-tolerant age- and BMI-matched men with CC genotype (age 53¿±¿6 years and BMI 26¿±¿3 kg/m2). Serum proinsulin, insulin, C-peptide and plasma glucose, glucagon, GLP-1, GLP-2 and GIP were obtained 0, 15, 30......Aims/hypothesis The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele associates with type 2 diabetes in several populations, possibly mediated via decreased incretin secretion and/or action and altered beta and alpha cell function. We aimed to study circulating levels of glucose......, 45, 60, 75, 90, 105, 120, 135, 150, 180, 210, and 240 min after ingestion of a standardised breakfast meal. Results An elevated incremental AUC for plasma glucose was observed among TT genotype carriers (CC carriers 21.8¿±¿101.9 mmol/l¿×¿min vs TT carriers 97.9¿±¿89.2 mmol/l¿×¿min, p¿=¿0.001). TT...

  5. Serum Ceramide Kinase as a Biomarker of Cognitive Functions, and the Effect of Using Two Slimming Dietary Therapies in Obese Middle Aged Females

    Science.gov (United States)

    Moaty, Maha I. A.; Fouad, Suzanne; El Shebini, Salwa M.; Kazem, Yusr M. I.; Ahmed, Nihad H.; Mohamed, Magda S.; Hussein, Ahmed M. S.; Arafa, Atiat M.; Hanna, Laila M.; Tapozada, Salwa T.

    2015-01-01

    AIM: Highlighting the impact of obesity on mental and cognitive functions using serum ceramide kinase enzyme concentration as a biomarker for cognitive evaluation in the middle aged females, and also targeting to control the obesity and simultaneously postponing the deterioration of the cognitive functions, by implementing two slimming dietary therapies each incorporating different functional ingredients known to boost cognition. SUBJECTS AND METHODS: Ninety six obese middle aged females, divided into two groups volunteered to follow a low caloric balanced diet combined with two bread supplements composed essentially of barley flour and wheat germ mixed with either 5% turmeric, group (A); or with 5% ginger, group (B) for 4 weeks, phase (1); to be followed by the hypocaloric diet alone for another 4 weeks, phase (2). RESULTS: By the end of phase (1), the biochemical analysis showed a positive response of the levels of C-peptide and modified homeostatic model assessment of insulin resistance; also increased levels of the serum ceramide kinase enzyme, coupled with improved cognitive functions tests. Improvement of the relevant metabolic profile, fasting blood glucose, blood pressure and the anthropometric measurements was detected. CONCLUSION: Using dietary therapy supported by special formulas which contain active ingredients succeeded in reducing weight and improving both the metabolic profile and the cognitive functions. PMID:27275191

  6. 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...

  7. Long-Term Survival of Neonatal Porcine Islets Without Sertoli Cells in Rabbits

    Directory of Open Access Journals (Sweden)

    Rafael Vald and eacute;s-Gonz and aacute;lez

    2013-04-01

    Full Text Available Cell-based therapy is a promising treatment for metabolic disorders such as type-1 diabetes. Transplantation protocols have investigated several anatomical sites for cell implantation; however, some of these procedures, such as intraportal infusion, can cause organ failure or thrombosis secondarily. Bio-artificial organs could be the choice, although concerns still remain. Using a subcutaneous device, we are able to preserve neonatal porcine islets without sertoli cells in healthy New Zealand rabbits. Devices were implanted in the back of the animals underneath the skin, and after 3 months the islets were transplanted. Histology showed the presence of inflammatory cells, predominantly eosinophils; however, insulin- and glucagon-positive cell clusters were identified inside the device at different time points for at least 90 days, and porcine C-peptide was also detected during the follow-up, indicating graft functionality. We have found that our device induces the deposition of a fibrous matrix enriched in blood vessels, which forms a good place for cell grafting, and this model is probably able to induce an immunoprivileged site. Under these conditions, transplanted porcine islet cells have the capability of producing insulin and glucagon for at least three months. [Arch Clin Exp Surg 2013; 2(2.000: 101-108

  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. 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

  10. The association between TNF-α and insulin resistance in euglycemic women.

    LENUS (Irish Health Repository)

    Walsh, Jennifer M

    2013-10-01

    Chronic low levels of inflammation have links to obesity, diabetes and insulin resistance. We sought to assess the relationship between cytokine tumor necrosis factor (TNF-α) and insulin resistance in a healthy, euglycemic population. This is a prospective study of 574 non-diabetic mother and infant pairs. Maternal body mass index (BMI), TNF-α, glucose and insulin were measured in early pregnancy and at 28 weeks. Insulin resistance was calculated by HOMA index. At delivery birthweight was recorded and cord blood analysed for fetal C-peptide and TNF-α. In a multivariate model, maternal TNF-α in early pregnancy was predicted by maternal insulin resistance at the same time-point, (β=0.54, p<0.01), and maternal TNF-α at 28 weeks was predicted by maternal insulin resistance in early pregnancy (β=0.24, p<0.01) and at 28 weeks (β=0.39, p<0.01). These results, in a large cohort of healthy, non-diabetic women have shown that insulin resistance, even at levels below those diagnostic of gestational diabetes, is associated with maternal and fetal inflammatory response. These findings have important implications for defining the pathways of fetal programming of later metabolic syndrome and childhood obesity.

  11. 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

  12. 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

  13. 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

  14. Differential induction, purification and characterization of cold active lipase from Yarrowia lipolytica NCIM 3639.

    Science.gov (United States)

    Yadav, K N Sathish; Adsul, M G; Bastawde, K B; Jadhav, D D; Thulasiram, H V; Gokhale, D V

    2011-11-01

    The production, purification and characterization of cold active lipases by Yarrowia lipolytica NCIM 3639 is described. The study presents a new finding of production of cell bound and extracellular lipase activities depending upon the substrate used for growth. The strain produced cell bound and extracellular lipase activity when grown on olive oil and Tween 80, respectively. The organism grew profusely at 20 °C and at initial pH of 5.5, producing maximum extracellular lipase. The purified lipase has a molecular mass of 400 kDa having 20 subunits forming a multimeric native protein. Further the enzyme displayed an optimum pH of 5.0 and optimum temperature of 25 °C. Peptide mass finger printing reveled that some peptides showed homologues sequence (42%) to Yarrowia lipolytica LIP8p. The studies on hydrolysis of racemic lavandulyl acetate revealed that extracellular and cell bound lipases show preference over the opposite antipodes of irregular monoterpene, lavandulyl acetate. PMID:21967715

  15. [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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired β-cell function in women with gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Lundberg, T. P.; Højlund, K.; Snogdal, L. S.;

    2015-01-01

    AIMS: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including β-cell function and insulin sensitivity. METHODS: During 1997-2010, 407...... women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin...... similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post...

  7. 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

  8. 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.)

  9. Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1*

    Science.gov (United States)

    Lee, Siyoung; Kim, Eunsom; Jhun, Hyunjhung; Hong, Jaewoo; Kwak, Areum; Jo, Seunghyun; Bae, Suyoung; Lee, Jongho; Kim, Busun; Lee, Jungmin; Youn, Sulah; Kim, Somi; Kim, Miyeon; Kim, Hyunwoo; Lee, Youngmin; Choi, Dong-Ki; Kim, Yong-Sung; Kim, Soohyun

    2016-01-01

    Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1. PMID:27226621

  10. Proinsulin Shares a Motif with Interleukin-1α (IL-1α) and Induces Inflammatory Cytokine via Interleukin-1 Receptor 1.

    Science.gov (United States)

    Lee, Siyoung; Kim, Eunsom; Jhun, Hyunjhung; Hong, Jaewoo; Kwak, Areum; Jo, Seunghyun; Bae, Suyoung; Lee, Jongho; Kim, Busun; Lee, Jungmin; Youn, Sulah; Kim, Somi; Kim, Miyeon; Kim, Hyunwoo; Lee, Youngmin; Choi, Dong-Ki; Kim, Yong-Sung; Kim, Soohyun

    2016-07-01

    Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1. PMID:27226621

  11. High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity.

    Science.gov (United States)

    Carlsson, E; Ludvigsson, J; Huus, K; Faresjö, M

    2016-04-01

    Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity. PMID:25892449

  12. Sleep Deficiency is a Modifiable Risk Factor for Obesity and Cognitive Impairment and Associated with Elevated Visfatin

    Science.gov (United States)

    Kazem, Yusr M. I.; Shebini, Salwa M. El; Moaty, Maha I. A.; Fouad, Suzanne; Tapozada, Salwa T.

    2015-01-01

    AIM: To study the interaction between sleep deprivation, obesity and cognitive functions, and the effect of following a balanced low caloric diet and increasing sleep duration on those variables. SUBJECTS AND METHODS: Ninety two obese females with mean age 47.00 ± 2.00 years and body mass index (BMI) 36.14 ± 3.00 kg/m² were divided into 3 groups according to their sleeping hours. They followed balanced low-caloric diet and were instructed to increase sleeping hours. Full clinical examination, 24 hours dietary intake recall, anthropometric measurements, mini mental state test, questionnaire for subjective sleep and life style evaluation were performed at baseline and after 2 months. Serum visfatin, fasting blood glucose and C-peptide were assessed; Modified homeostatic model assessment of insulin resistance was calculated. RESULTS: About one third of our sample slept less than 6 hours daily, group (1), all patients had elevated visfatin serum level (33.87 ± 2.8 ng/ml) with the highest level in group (1). At base line, group (1) showed the highest BMI, lowest cognitive functions, highest visfatin level and highest insulin resistance (P sleep duration (P Sleep deprivation may be a modifiable risk factor for obesity, cognitive impairment and visfatin elevation.

  13. Reduction in Endogenous Insulin Secretion is a Risk Factor of Sarcopenia in Men with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Tanaka, Ken-ichiro; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2015-10-01

    Sarcopenia has recently attracted widespread attention, because it increases risks of fall and bedridden. Although patients with type 2 diabetes mellitus (T2DM) are known to have lower muscle mass of limbs than healthy people, the mechanism is still unclear. We thus examined the association of muscle mass with parameters of endogenous insulin secretion such as fasting immunoreactive insulin, fasting C-peptide immunoreactivity (CPR), and daily urine CPR in 191 men with T2DM. Muscle mass of arms and legs was evaluated by dual-energy X-ray absorptiometry, and we calculated relative skeletal muscle index (RSMI), which is useful for the diagnosis of sarcopenia. Multiple regression analyses adjusted for age, duration of T2DM, serum creatinine, HbA1c, and insulin-like growth factor-I showed that each parameter of endogenous insulin was significantly and positively correlated with muscle mass of arms and legs as well as RSMI (p sarcopenia than those without it (p sarcopenia in men with T2DM. PMID:25850525

  14. 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

  15. Immune biomarkers in immunotherapeutic trials for type 1 diabetes: cui prodest?

    Science.gov (United States)

    Culina, S; Mallone, R

    2012-11-01

    Decades of research efforts aimed at upgrading type 1 diabetes (T1DM) treatment did not harvest much success besides improving insulin therapy, which remains the standard of care since 1922. Immunological strategies targeting autoimmune mechanisms, rather than their metabolic consequences, are highly demanded. A dealt of preclinical studies in animal models offered some promises, which were however not maintained once translated into human. All these immune intervention trials evaluated metabolic and clinical endpoints, namely C-peptide secretion, HbA(1c) and insulin requirements. While critical, we argue that these endpoints are insufficient and should be complemented with immune surrogate endpoints, i.e. biomarkers reflecting the immune modifications induced by such treatments. This is even more critical when clinical expectations are not met, in order to sort out the reasons of such failure, i.e. whether immune changes are not accomplished or whether, despite being accomplished, they are insufficient to translate into clinical benefits. Furthermore, these ancillary analyses may give precious indications to design further trials, i.e. to enroll patients with the best odds to respond to therapy and to follow-up their response. PMID:22858113

  16. Short-term subcutaneous insulin treatment delays but does not prevent diabetes in NOD mice.

    Science.gov (United States)

    Brezar, Vedran; Culina, Slobodan; Gagnerault, Marie-Claude; Mallone, Roberto

    2012-06-01

    Despite encouraging results in the NOD mouse, type 1 diabetes prevention trials using subcutaneous insulin have been unsuccessful. To explain these discrepancies, 3-week-old NOD mice were treated for 7 weeks with subcutaneous insulin at two different doses: a high dose (0.5 U/mouse) used in previous mouse studies; and a low dose (0.005 U/mouse) equivalent to that used in human trials. Effects on insulitis and diabetes were monitored along with immune and metabolic modifications. Low-dose insulin did not have any effect on disease incidence. High-dose treatment delayed but did not prevent diabetes, with reduced insulitis reappearing once insulin discontinued. This effect was not associated with significant immune changes in islet infiltrates, either in terms of cell composition or frequency and IFN-γ secretion of islet-reactive CD8(+) T cells recognizing the immunodominant epitopes insulin B(15-23) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214). Delayed diabetes and insulitis were associated with lower blood glucose and endogenous C-peptide levels, which rapidly returned to normal upon treatment discontinuation. In conclusion, high- but not low-dose prophylactic insulin treatment delays diabetes onset and is associated with metabolic changes suggestive of β-cell "rest" which do not persist beyond treatment. These findings have important implications for designing insulin-based prevention trials. PMID:22678909

  17. Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [3-3H]glucose studies in healthy subjects

    International Nuclear Information System (INIS)

    To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45mU/kg · min or in identical amounts in pulses of 11/2 to 21/4 min followed by intervals of 101/2 to 93/4 min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270-294 min: 8.7±0.7 vs 6.8±0.9 ml/kg · min, P 3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion. (author)

  18. Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients

    DEFF Research Database (Denmark)

    Samocha-Bonet, Dorit; Wong, Olivia; Synnott, Emma-Leigh;

    2011-01-01

    Impaired glucagon-like peptide (GLP-1) secretion or response may contribute to ineffective insulin release in type 2 diabetes. The conditionally essential amino acid glutamine stimulates GLP-1 secretion in vitro and in vivo. In a randomized, crossover study, we evaluated the effect of oral...... glutamine, with or without sitagliptin (SIT), on postprandial glycemia and GLP-1 concentration in 15 type 2 diabetes patients (glycated hemoglobin 6.5 ± 0.6%). Participants ingested a low-fat meal (5% fat) after receiving either water (control), 30 g l-glutamine (Gln-30), 15 g L-glutamine (Gln-15), 100 mg...... SIT, or 100 mg SIT and 15 g L-glutamine (SIT+Gln-15). Studies were conducted 1-2 wk apart. Blood was collected at baseline and postprandially for 180 min for measurement of circulating glucose, insulin, C-peptide, glucagon, and total and active GLP-1. Gln-30 and SIT+Gln-15 reduced the early (t = 0...

  19. Design, Synthesis, and Application of OB2C Combinatorial Peptide and Peptidomimetic Libraries

    Science.gov (United States)

    Liu, Ruiwu; Shih, Tsung-Chieh; Deng, Xiaojun; Anwar, Lara; Ahadi, Sara; Kumaresan, Pappanaicken; Lam, Kit S.

    2015-01-01

    The “one-bead two-compound” (OB2C) combinatorial library is constructed on topologically segregated trifunctional bilayer beads such that each bead has a fixed cell-capturing ligand and a random library compound co-displayed on its surface and a chemical coding tag (bar code) inside the bead. An OB2C library containing thousands to millions of compounds can be synthesized and screened concurrently within a short period of time. When live cells are incubated with such OB2C libraries, every bead will be coated with a monolayer of cells. The cell membranes of the captured cells facing the bead surface are exposed to the library compounds tethered to each bead. A specific biochemical or cellular response can be detected with an appropriate reporter system. The OB2C method enables investigators to rapidly discover synthetic molecules that not only interact with cell-surface receptors but can also stimulate or inhibit downstream cell signaling. To demonstrate this powerful method, one OB2C peptide library and two OB2C peptidomimetic libraries were synthesized and screened against Molt-4 lymphoma cells to discover “death ligands.” Apoptosis of the bead-bound cells was detected with immunocytochemistry using horseradish peroxidase (HRP)-conjugated anti-cleaved caspase-3 antibody and 3,3′-diaminobenzidine as a substrate. Two novel synthetic “death ligands” against Molt-4 cells were discovered using this OB2C library approach. PMID:25616322

  20. 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

  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. 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...... eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P <0.......01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703...

  3. 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)

  4. The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects

    Science.gov (United States)

    Tschritter, Otto; Rogic, Maja; Heni, Martin; Stingl, Katarina; Hallschmid, Manfred; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert; Hennige, Anita M.

    2011-01-01

    Background Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named “cerebral insulin resistance”, is responsible for overeating and the development of obesity. Methodology/Principal Findings To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream) in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. Conclusions/Significance We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a “cerebral insulin resistance” in obese subjects and might be relevant in the pathogenesis of obesity. PMID:21589921

  5. Sequence of a New World primate insulin having low biological potency and immunoreactivity

    International Nuclear Information System (INIS)

    The organization of the insulin gene of the owl or night monkey (Aotus trivirgatus), a New World primate, is similar to that of the human gene. The sequences of these two genes and flanking regions possess 84.3% homology. An unusual feature of the owl monkey gene is the partial duplication and insertion of a portion of the A-chain coding sequence into the 3' untranslated region. The insulin gene of this primate also lacks a region of tandem repeats that is present in the 5' flanking region of the human and chimpanzee genes. Owl monkey preproinsulin has 85.5% identity with the human insulin precursor and is the most divergent of the primate insulins/preproinsulins yet described. The differences between owl monkey and human preproinsulin include three substitutions in the signal peptide, two in the B chain, seven in the C peptide, and three in the A chain. One of these replacements is the conservative substitution of valine for isoleucine a position A2, an invariant site in all other vertebrate insulins and insulin-like growth factors. The substitutions in owl monkey insulin at B9, B27, A2, A4, and A17 alter its structure so that it has only 20% of the receptor-binding activity and 1% of the affinity with guinea pig anti-porcine insulin antibodies as compared to human insulin

  6. Sequence of a New World primate insulin having low biological potency and immunoreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Seino, S.; Steiner, D.F.; Bell, G.I.

    1987-11-01

    The organization of the insulin gene of the owl or night monkey (Aotus trivirgatus), a New World primate, is similar to that of the human gene. The sequences of these two genes and flanking regions possess 84.3% homology. An unusual feature of the owl monkey gene is the partial duplication and insertion of a portion of the A-chain coding sequence into the 3' untranslated region. The insulin gene of this primate also lacks a region of tandem repeats that is present in the 5' flanking region of the human and chimpanzee genes. Owl monkey preproinsulin has 85.5% identity with the human insulin precursor and is the most divergent of the primate insulins/preproinsulins yet described. The differences between owl monkey and human preproinsulin include three substitutions in the signal peptide, two in the B chain, seven in the C peptide, and three in the A chain. One of these replacements is the conservative substitution of valine for isoleucine a position A2, an invariant site in all other vertebrate insulins and insulin-like growth factors. The substitutions in owl monkey insulin at B9, B27, A2, A4, and A17 alter its structure so that it has only 20% of the receptor-binding activity and 1% of the affinity with guinea pig anti-porcine insulin antibodies as compared to human insulin.

  7. Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin

    Directory of Open Access Journals (Sweden)

    Resham R Poudel

    2012-01-01

    Full Text Available Approximately 10% of phenotypic type 2 diabetics have islet autoantibodies and are referred to as having latent autoimmune diabetes of adults (LADA, and they land on early sulfonylurea failure and require insulin. Diagnosing LADA has treatment implications because of high risk of progression to insulin dependency. But often there is delay in insulin therapy, as there are no recommendations for islet antibody testing in adult-onset diabetes currently. LADA clinical risk score can identify adults at high risk who may benefit from antibody testing. The optimal treatment of LADA is not established. Early insulin therapy helps to achieve good metabolic control and better long-term outcomes by preserving b-cells and endogenous C-peptide secretion. Sulfonylureas are better avoided as they exhaust b-cells; glitazones and exenatide have favorable outcomes, whereas metformin needs to be used with caution. Understanding LADA will also bring new windows in managing type 1 diabetes. Information acquisition was done by reviewing the medical literature published since 1987, with particular attention to the natural history, genetic factors, and treatment of LADA.

  8. Hydrothermally modified slow release corn starch: a potential new therapeutic option for treating hypoglycemia in autoimmune hypoglycemia (Hirata's disease).

    Science.gov (United States)

    Lechner, K; Aulinger, B; Brand, S; Waldmann, E; Parhofer, K G

    2015-12-01

    We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone. PMID:26373963

  9. 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.

  10. Glucose-stimulated prehepatic insulin secretion is associated with circulating alanine, triglyceride, glucagon, lactate and TNF-alpha in patients with HIV-lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Pedersen, S B; Dela, F; Deacon, C F; Holst, Jens Juul; Iversen, J; Madsbad, S

    2006-01-01

    lipodystrophic HIV-infected (LIPO) patients and 25 normoglycaemic nonlipodystrophic HIV-infected patients (controls) were included in the study. The prehepatic insulin secretion rate was estimated by deconvolution of C-peptide concentrations, and insulin sensitivity (SIRd) was estimated by the glucose clamp...... technique. The disposition index (Di=ISREG0-10 min x SIRd) was calculated to estimate the beta-cell response relative to insulin sensitivity. RESULTS: FISR was increased by 69% (P<0.001), whereas median Di was decreased by 75% (P<0.01), primarily as a result of a reduction of SI(Rd) by 60% (P<0.001) in LIPO...... patients compared with controls. Three LIPO groups were identified arbitrarily according to their FISR and ISREG0-10 min values relative to those of controls. Four LIPO patients displayed high FISR [+3 standard deviations (SD), P<0.001], high ISREG0-10 min (+3 SD, P<0.001) and low SIRd (P<0.01), suggesting...

  11. Glucose-stimulated prehepatic insulin secretion is associated with circulating alanine, triglyceride, glucagons, lactate and TNF-alfa in patients with HIV-lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Pedersen, SB; Dela, Flemming; Holst, JJ; Deacon, C; Iversen, Johan; Madsbad, Sten

    2006-01-01

    lipodystrophic HIV-infected (LIPO) patients and 25 normoglycaemic nonlipodystrophic HIV-infected patients (controls) were included in the study. The prehepatic insulin secretion rate was estimated by deconvolution of C-peptide concentrations, and insulin sensitivity (SIRd) was estimated by the glucose clamp...... technique. The disposition index (Di=ISREG0-10 min x SIRd) was calculated to estimate the beta-cell response relative to insulin sensitivity. RESULTS: FISR was increased by 69% (P<0.001), whereas median Di was decreased by 75% (P<0.01), primarily as a result of a reduction of SI(Rd) by 60% (P<0.001) in LIPO...... patients compared with controls. Three LIPO groups were identified arbitrarily according to their FISR and ISREG0-10 min values relative to those of controls. Four LIPO patients displayed high FISR [+3 standard deviations (SD), P<0.001], high ISREG0-10 min (+3 SD, P<0.001) and low SIRd (P<0.01), suggesting...

  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 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. PMID:26881248

  13. 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.

  14. 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.

  15. 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.

  16. Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance

    DEFF Research Database (Denmark)

    Muscelli, Elza; Mari, Andrea; Natali, Andrea;

    2006-01-01

    The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolu......The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C......-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of beta-cell glucose sensitivity (OGTT/IV ratio = 1.73 +/- 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered......, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of beta-cell function, particularly beta-cell glucose sensitivity. In IGT, beta...

  17. Serum TNF-Alpha Level Predicts Nonproliferative Diabetic Retinopathy in Children

    Directory of Open Access Journals (Sweden)

    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.

  18. A Study of the Variation in the Salivary Peptide Profiles of Young Healthy Adults Acquired Using MALDI-TOF MS

    Science.gov (United States)

    Brand, Henk; Imangaliyev, Sultan; Tsivtsivadze, Evgeni; van der Weijden, Fridus; de Jong, Ad; Paauw, Armand; Crielaard, Wim; Keijser, Bart; Veerman, Enno

    2016-01-01

    A cross-sectional observational study was conducted to evaluate the inter-individual variation in the MALDI-TOF MS peptide profiles of unstimulated whole saliva in a population of 268 systemically healthy adults aged 18–30 yr (150 males and 118 females) with no apparent caries lesions or periodontal disease. Using Spectral Clustering, four subgroups of individuals were identified within the study population. These subgroups were delimited by the pattern of variation in 9 peaks detected in the 2–15 kDa m/z range. An Unsupervised Feature Selection algorithm showed that P-C peptide, a 44 residue-long salivary acidic proline-rich protein, and three of its fragments (Fr. 1–25, Fr. 15–35 and Fr. 15–44) play a central role in delimiting the subgroups. Significant differences were found in the salivary biochemistry of the subgroups with regard to lysozyme and chitinase, two enzymes that are part of the salivary innate defense system (p < 0.001). These results suggest that MALDI-TOF MS salivary peptide profiles may relate information on the underlying state of the oral ecosystem and may provide a useful reference for salivary disease biomarker discovery studies. PMID:27258023

  19. High fasting serum insulin level due to autoantibody interference in insulin immunoassay discloses autoimmune insulin syndrome: a case report.

    Science.gov (United States)

    Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric

    2016-08-01

    Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome. PMID:27492703

  20. Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID) mouse necessitates anti-CD3 preactivation of human immune cells

    Science.gov (United States)

    Gysemans, C; Waer, M; Laureys, J; Depovere, J; Pipeleers, D; Bouillon, R; Mathieu, C

    2000-01-01

    Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool for research in transplantation. The aim of this study was to define the conditions necessary for a reconstituted human immune system to destroy in a consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse. We examined different time points of hu-PBL reconstitution, different transplantation sites of the islets and several hu-PBL reconstitution protocols. Major differences in graft destruction were observed between the different hu-PBL reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site of transplantation. Although preactivation of hu-PBL did not improve the level of hu-PBL chimerism, histological and immunohistochemical analysis of the grafts revealed a severe human lymphocytic infiltration and β cell destruction only in the grafts of mice receiving preactivated hu-PBL. This β cell injury resulted in impaired glucose tolerance, with in some animals recurrence of hyperglycaemia, and decreased insulin and C-peptide levels after glucose stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID mice. The need for immune manipulation suggests that interactions between hu-PBL and xenografts in this model may be hampered by incompatibilities in cross-species adhesion and/or activation signals. PMID:10971525

  1. Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans

    DEFF Research Database (Denmark)

    Ahrén, Bo; Holst, Jens Juul; Mari, Andrea

    2003-01-01

    have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS: Eight women (aged 69 years, fasting glucose 3.7-10.3 mmol/l, BMI 22.4-43.9 kg/m(2)) who had fasted...... overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol x kg(-1) x min(-1)), and beta-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS......: -GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 +/- 4.2 nmol/m(2) with GLP-1 versus 21.0 +/- 1.6 nmol/m(2) with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 +/- 26 with GLP...

  2. Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lotte B; Ploug, Kenneth B; Swift, Peter;

    2007-01-01

    OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing and normal glucagon and insulin secretion from pancreatic endocrine alpha- and beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing cells secreting glucagon-like peptide-1 (GLP-1) and glucose...... on glucose-sensing tissues in vivo that may affect the overall glycaemic control in children with new-onset type 1 diabetes. DESIGN AND METHODS: Western blot and immunohistochemical analyses were performed for expression and co-localisation studies. Meal-stimulated C-peptide test was carried out in...... 12 month study period (coefficient = 0.42%, P = 0.03). CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit Kir6.2 may cause defective glucose sensing in several tissues and impaired glycaemic control...

  3. 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. PMID:25900579

  4. Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes.

    Science.gov (United States)

    Yang, Kaiyuan; Gotzmann, Jonathan; Kuny, Sharee; Huang, Hui; Sauvé, Yves; Chan, Catherine B

    2016-06-01

    We compared the evolution of insulin resistance, hyperglycemia, and pancreatic β-cell dysfunction in the Nile rat (Arvicanthis niloticus), a diurnal rodent model of spontaneous type 2 diabetes (T2D), when maintained on regular laboratory chow versus a high-fiber diet. Chow-fed Nile rats already displayed symptoms characteristic of insulin resistance at 2 months (increased fat/lean mass ratio and hyperinsulinemia). Hyperglycemia was first detected at 6 months, with increased incidence at 12 months. By this age, pancreatic islet structure was disrupted (increased α-cell area), insulin secretion was impaired (reduced insulin secretion and content) in isolated islets, insulin processing was compromised (accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells. By contrast, high-fiber-fed Nile rats had normoglycemia with compensatory increase in β-cell mass resulting in maintained pancreatic function. Fasting glucose levels were predicted by the α/β-cell ratios. Our results show that Nile rats fed chow recapitulate the five stages of progression of T2D as occurs in human disease, including insulin-resistant hyperglycemia and pancreatic islet β-cell dysfunction associated with ER stress. Modification of diet alone permits long-term β-cell compensation and prevents T2D. PMID:27068697

  5. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats.

    Science.gov (United States)

    Suman, Rajesh Kumar; Ray Mohanty, Ipseeta; Borde, Manjusha K; Maheshwari, Ujwala; Deshmukh, Y A

    2016-01-01

    Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component. PMID:26880906

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

    Science.gov (United States)

    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

    2014-01-01

    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 concentration dependence of L-Trp-mediated tna operon induction, whereas the TnaC I19L change suppresses this phenotype, restoring the sensitivity of the translating A2058U mutant ribosome to free L-Trp. These findings suggest that interactions between TnaC residue I19 and 23S rRNA nucleotide A2058 contribute to the creation of a regulatory L-Trp binding site within the translating ribosome. PMID:24137004

  7. Diabetes mellitus in a domesticated Spanish mustang.

    Science.gov (United States)

    Johnson, Philip J; Scotty, Nicole C; Wiedmeyer, Charles; Messer, Nat T; Kreeger, John M

    2005-02-15

    An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the baseline concentration until 5 hours after i.v. administration of a glucose bolus, suggesting that insulin secretion, insulin effect, or both were reduced. However, i.v. administration of insulin caused only a slight decrease in the plasma glucose concentration, giving the impression that the action of insulin was impaired. Within 5 hours after administration of a combination of glyburide and metformin, which is used to treat diabetes mellitus in humans, the glucose concentration was within reference limits. The horse was euthanized, and a postmortem examination was done. Immunohistochemical staining of sections of the pancreas revealed attenuation of the pancreatic islet beta-cell population, with beta cells that remained generally limited to the periphery of the islets. These findings indicate that, albeit rare, pancreatic beta-cell failure may contribute to the development of diabetes mellitus in horses. PMID:15742701

  8. Middle-Preserving Pancreatectomy for Multifocal Metastatic Renal Cell Carcinoma Located in the Head, Body and Tail of the Pancreas. A Case Report

    Directory of Open Access Journals (Sweden)

    Hiroki Ohzato

    2010-11-01

    Full Text Available Context Postoperative endocrine and exocrine insufficiencies following traditional pancreatectomies might cause a deterioration of the quality of life and surgical outcome. Parenchyma-sparing pancreatectomies have been utilized in benign lesions and low-grade malignancies. Case report A 67-year-old female with a past history of right nephrectomy for renal cell carcinoma 20 years earlier was referred to our institute with obstructive jaundice and multiple nodules in the pancreas. Computed tomography demonstrated five well-demarcated, strongly enhanced nodules with diameters of 5.5 cm in the head, 2.0 and 1.8 cm in the body, and 1.2 and 1.0 cm in the tail. Fluorine-18 fluorodeoxyglucose positron emission tomography did not demonstrate any extrapancreatic uptake. A middle-preserving pancreatectomy was performed after ultrasonography had confirmed arterial perfusion in the middle segment. A histological study demonstrated metastatic clear cell renal carcinoma. To date, the patient has remained without recurrence for two and a half years since surgery. A minimal administration of insulin has been necessary; however, C-peptide is detectable and nutritional status is comparatively good. Conclusion A middle-preserving pancreatectomy is a useful procedure in a parenchymasparing pancreatectomy for resecting multifocal lesions in the head, body and tail of the pancreas.

  9. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    Science.gov (United States)

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. PMID:25407640

  10. Prevalence of elevated C-reactive protein among newly diagnosed type 2 diabetes patients in Denmark: Results from the population-based DD2 study

    DEFF Research Database (Denmark)

    Thomsen, Reimar W.; Mor, Anil; Rungby, Jørgen;

    .01), higher fasting blood glucose (7.26 vs. 6.82 mmol/L, p<0.0001), higher C-peptide (784 vs. 545, p<0.0001), and were more likely to be on insulin treatment (7.7% vs. 5.0%, prevalence ratio 1.54 (95% CI: 0.96-2.13). Blood pressure, lipids, and current smoking were similar between groups. Patients with high...... diagnosed T2D patients in Denmark, 19.6% had CRP values of more than 6 mg/L. Patients in the highest CRP tertile were more likely to be female, obese, physically inactive, and comorbid, with worse blood glucose control compared to those with low CRP.......Objectives: Levels of high-sensitivity C-reactive protein (CRP) are increased in patients with prevalent type 2 diabetes (T2D) and may predict coronary heart disease. There is limited knowledge of CRP levels among newly diagnosed T2D patients in the population-based setting. We determined the...

  11. Severe suicidal digoxin and propranolol toxicity with insulin overdose

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    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.

  12. Serum Levels of Osteocalcin and Insulin Resistance in Patients with Impaired Glucose Tolerance or New-Onset Diabetes Mellitus After Liver Transplantation.

    Science.gov (United States)

    Martínez-Díaz-Guerra, G; Guadalix, S; Aramendi, M; Librizzi, S; García, E; Jiménez, C; Hawkins, F

    2016-05-01

    Liver transplantation (LT) patients are at high risk of developing new-onset diabetes after transplantation (NODAT). Osteocalcin has been proposed as a mediator between bone tissue and glucose metabolism, but its role in the pathogenesis of diabetes is not defined yet. Our objective was to assess the relationship between serum osteocalcin and glucose metabolism parameters in liver transplantation recipients. A total of 187 liver transplantation patients were cross-sectionally studied, 54 of them developed NODAT. None had been diagnosed of diabetes mellitus prior to transplant. In 133 nondiabetic patients, a 75 g oral glucose tolerance test (OGTT) was performed to assess blood glucose, insulin, and C-peptide levels at baseline and 120 min. Serum total osteocalcin was measured at baseline in all patients.After OGTT, 10.5% of LT patients had NODAT criteria, 51.9% showed impaired glucose tolerance, and 37.6% had normal glucose tolerance. Overall, NODAT prevalence was 36.3%. HOMA-IR was significantly higher in NODAT compared with impaired glucose tolerance and normal glucose tolerance groups (pliver transplantation patients and is associated with insulin resistance. In these patients total osteocalcin is inversely associated with plasma glucose level and insulin resistance indexes. PMID:26743527

  13. Cardiovascular autonomic neuropathy in insulin-dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in the general population

    DEFF Research Database (Denmark)

    May, O; Arildsen, H; Damsgaard, E M;

    2000-01-01

    OBJECTIVES: The aim of the study was to estimate the prevalence of cardiovascular autonomic neuropathy (CAN) in Type 1 diabetes mellitus in the general population and to assess the relationship between CAN and risk of future coronary heart disease (CHD). METHODS: The Type 1 diabetes mellitus...... population in the municipality of Horsens, Denmark, was delineated by the prescription method and a random sample of 120 diabetics aged 40-75 years was recruited. Type 1 diabetes mellitus was registered if fasting C-peptide was below 0.30 nmol L(-1). The E/I ratio was calculated as the mean of the longest R......, was computed. Additionally, the 10-year risk of CHD was calculated using the Framingham model. RESULTS: A total of 84 people responded, of whom 71 had Type 1 diabetes mellitus. The E/I ratio was measured in 69 people. The prevalence of CAN expressed as an E/I ratio below the normal 5th percentile was...

  14. Changes in Plasma Levels of N-Arachidonoyl Ethanolamine and N-Palmitoylethanolamine following Bariatric Surgery in Morbidly Obese Females with Impaired Glucose Homeostasis

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    Akhila Mallipedhi

    2015-01-01

    Full Text Available Aim. We examined endocannabinoids (ECs in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG and endocannabinoid-related lipids (PEA, OEA. Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r=0.55, P=0.01, HOMA-IR (r=0.61, P=0.009, and HOMA %S (r=-0.71, P=0.002. OEA was correlated with weight (r=0.49, P=0.03, waist circumference (r=0.52, P=0.02, fasting insulin (r=0.49, P=0.04, and HOMA-IR (r=0.48, P=0.05. PEA was correlated with fasting insulin (r=0.49, P=0.04. 2-AG had a negative correlation with fasting glucose (r=-0.59, P=0.04. Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis.

  15. An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.

    Science.gov (United States)

    Rivas, Eric; Newmire, Dan E; Crandall, Craig G; Hooper, Philip L; Ben-Ezra, Vic

    2016-07-01

    Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45±7.1% fat mass) type 2 diabetics (T2DM: 50.1±12y, 7.5±1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1±13.7y) healthy non-obese controls (HC: 33.4±7.8% fat mass, Pleptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg·fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. PMID:27264884

  16. 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.

  17. 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

  18. 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

  19. High plasma levels of islet amyloid polypeptide in young with new-onset of type 1 diabetes mellitus.

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    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.

  20. PREVALENCE OF TESTOSTERONE DEFICIENCY IN PATIENTS OF DIABETES MELLITUS LESS THAN 40 YEARS OF AGE

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    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.

  1. 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

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    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.

  2. 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

  3. Nanomaterials enhance osteogenic differentiation of human mesenchymal stem cells similar to a short peptide of BMP-7

    Directory of Open Access Journals (Sweden)

    Lock J

    2011-11-01

    Full Text Available Jaclyn Lock, Huinan Liu Department of Bioengineering, University of California, Riverside, CA, USA Background: Nanomaterials have unique advantages in controlling stem cell function due to their biomimetic characteristics and special biological and mechanical properties. Controlling adhesion and differentiation of stem cells is critical for tissue regeneration. Methods: This in vitro study investigated the effects of nano-hydroxyapatite, nano-hydroxyapatite-polylactide-co-glycolide (PLGA composites, and a bone morphogenetic protein (BMP-7-derived short peptide (DIF-7c on osteogenic differentiation of human mesenchymal stem cells (MSC. The peptide was chemically functionalized onto nano-hydroxyapatite, incorporated into a nanophase hydroxyapatite-PLGA composite or PLGA control, or directly injected into culture media. Results: Unlike the PLGA control, the nano-hydroxyapatite-PLGA composites promoted adhesion of human MSC. Importantly, nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites promoted osteogenic differentiation of human MSCs, comparable with direct injection of the DIF-7c peptide into culture media. Conclusion: Nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites provide a promising alternative in directing the adhesion and differentiation of human MSC. These nanocomposites should be studied further to clarify their effects on MSC functions and bone remodeling in vivo, eventually translating to clinical applications. Keywords: human mesenchymal stem cells, osteogenesis, stem cell differentiation, bone morphogenetic protein, peptide delivery, nanocomposites

  4. 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. PMID:26944483

  5. The Effects of Synthetic Oligopeptide Derived from Enamel Matrix Derivative on Cell Proliferation and Osteoblastic Differentiation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Nobuhito Katayama

    2014-08-01

    Full Text Available Enamel matrix derivative (EMD is widely used in periodontal tissue regeneration therapy. However, because the bioactivity of EMD varies from batch to batch, and the use of a synthetic peptide could avoid use from an animal source, a completely synthetic peptide (SP containing the active component of EMD would be useful. In this study an oligopeptide synthesized derived from EMD was evaluated for whether it contributes to periodontal tissue regeneration. We investigated the effects of the SP on cell proliferation and osteoblast differentiation of human mesenchymal stem cells (MSCs, which are involved in tissue regeneration. MSCs were treated with SP (0 to 1000 ng/mL, to determine the optimal concentration. We examined the effects of SP on cell proliferation and osteoblastic differentiation indicators such as alkaline phosphatase activity, the production of procollagen type 1 C-peptide and osteocalcin, and on mineralization. Additionally, we investigated the role of extracellular signal-related kinases (ERK in cell proliferation and osteoblastic differentiation induced by SP. Our results suggest that SP promotes these processes in human MSCs, and that ERK inhibitors suppress these effects. In conclusion, SP promotes cell proliferation and osteoblastic differentiation of human MSCs, probably through the ERK pathway.

  6. Cognitive functions in middle aged individuals are related to metabolic disturbances and aerobic capacity: a cross-sectional study.

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    Maria Pedersen

    Full Text Available AIMS: Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals. METHODS: We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56, age-matched individuals with impaired glucose tolerance (N = 56 as well as age-matched controls with normal glucose tolerance (N = 72. Specific cognitive functions were assessed with focus on verbal memory, processing speed, executive functions, and a composite overall mean score. Oral glucose tolerance test, VO(2max test, systemic inflammation, DXA scanning and abdominal MRI were measured. RESULTS: Multiple linear regression analyses adjusting for age, gender and verbal intelligence demonstrated that a low score in processing speed, executive functions and overall cognitive function were related to high fasting C-peptide, as well as low insulin sensitivity, beta-cell function and VO(2max. Measurements of blood glucose, obesity and inflammation were not associated with cognitive function. CONCLUSION: Low cognitive scores are seen in middle aged individuals with hyperinsulinemia, low insulin sensitivity, beta-cell function and low aerobic capacity. These findings emphasize the importance of appropriate lifestyle and not only blood glucose control in prevention of cognitive disability.

  7. 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

  8. Conditioned insulin and blood sugar responses in humans in relation to binge eating.

    Science.gov (United States)

    Overduin, J; Jansen, A

    1997-04-01

    This study proposed to demonstrate a classically conditioned blood sugar decrease in humans and to clarify its relevance for binge eating. Six conditioning trials were run in healthy females. The conditioned stimulus (CS) was a compound peppermint flavor/fragrance, whereas the unconditioned stimulus (UCS) consisted of 50 g of oral glucose. Control subjects received an aspartame drink as the UCS. Ad lib glucose intake, blood parameters, and subjective craving were monitored before and after conditioning. Results showed that the experimental group failed to show conditioned blood sugar and glucagon decreases or C-Peptide increases. Although an increased insulin response was found in the experimental group, the effect size did not exceed that of spontaneous fluctuations. No increases in craving for sweet substances were found. An impressive increase (mean: 78%) in glucose intake after conditioning was found in both conditions, as well as in a subsequently run third condition with plain water as the UCS. The increased glucose intake probably resulted from an initial neophobia to the laboratory setting that subsided as subjects had experienced more lab sessions. Importantly, because no conditioned hypoglycemia occurred in the present study, its relationship with subjectively experienced craving for sweet substance could not be determined. PMID:9108577

  9. Cephalic phase metabolic responses in normal weight adults.

    Science.gov (United States)

    Bruce, D G; Storlien, L H; Furler, S M; Chisholm, D J

    1987-08-01

    The presence and physiologic importance of cephalic phase insulin release in humans remains controversial. The aim of these studies was to determine whether cephalic phase insulin release could be demonstrated in normal weight subjects and whether it would be associated with changes in blood glucose, free fatty acid, and pancreatic polypeptide levels. The studies were followed by a hyperglycemic clamp to determine whether cephalic responses would alter overall glucose disposal or glucose-stimulated insulin secretion. In all, 17 subjects were studied on two occasions with and without (control study) presentation of food stimuli. Tease-feeding alone (n = 6), or the administration of a sweet taste alone (aspartame, n = 5) failed to stimulate cephalic responses. However, the presentation of the combined stimuli (tease meals plus sweet taste, n = 7) resulted in a significant fall (P less than .005) in blood glucose levels and a variable rise in serum insulin (% insulin rise 38 +/- 15%, P less than .05) and C-peptide levels (7 +/- 6%, NS) within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly (r = .90, P less than .01) with a score of the subjective response to the food and taste.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3298939

  10. Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice.

    Science.gov (United States)

    Kenngott, Elisabeth E; Cole, Sally; Hein, Wayne R; Hoffmann, Ute; Lauer, Uta; Maass, David; Moore, Lloyd; Pfeil, Jennifer; Rosanowski, Sarah; Shoemaker, Charles B; Umair, Saleh; Volkmer, Rudolf; Hamann, Alf; Pernthaner, Anton

    2016-01-01

    In this study we identified and characterized a novel cyclic peptide that facilitates the rapid transportation of conjugated molecules across the epithelial layer of the small intestine. The peptide was initially selected from phage display libraries using a large animal experimental model, which employed consecutive in vitro and in vivo panning. The procedure was designed to enrich for peptides that facilitated transcytosis across the intestinal epithelium into the intestinal afferent lymphatic system. A small set of peptides was repeatedly isolated using this selection method; however, the cyclic nonamer CTANSSAQC, 13C, dominated. The activity of the putative targeting peptide 13C was then verified using a mouse model. These experiments showed that the 13C peptide as well as macromolecules conjugated to it were rapidly transported across the intestinal mucosa into distinct subsets of epithelial cells and CD11c+ cells located in the lamina propria and Peyer's Patches. Significant amounts of intact protein could be delivered into the systemic circulation after rectal and nasal application. Thus, peptide 13C is regarded as an attractive carrier candidate for mucosal delivery of large molecules. The preferential targeting to distinct intestinal cells may be utilized to deliver active biological drugs for the effective control of diseases of the gut. PMID:26568284

  11. Effects of piragliatin, a glucokinase activator, on fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Zhi, Jianguo; Zhai, Suoping

    2016-02-01

    To assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of piragliatin, a double-blind, randomized, placebo-controlled, multiple-ascending-doses study was conducted in patients with type 2 diabetes mellitus (T2D). Fifty-nine T2D patients were given piragliatin or placebo in a dose-escalation design as a single dose on day 1 followed by multiple doses on days 3 through 8 at doses of 10, 25, 50, 100, and 200 mg twice a day (BID) as well as 200 mg every day (QD). Blood and urine samples were collected for PK analysis. PD assessments included plasma glucose, insulin, C-peptide, glucagon, and GLP-1. Piragliatin exposure was dose proportional without appreciable accumulation or food effect. Piragliatin treatment at steady state yielded dose-dependent reductions up to 32.5% and 35.5% for the highest dose in fasting and postprandial plasma glucose. Piragliatin was well tolerated. Mild or moderate hypoglycemia with rapid recovery after sugar-containing drinks or scheduled meals was the only dose-limiting adverse event. It is concluded that multiple doses of piragliatin consistently showed rapid, dose-dependent glucose reduction of fasting and postprandial plasma glucose in T2D patients. PMID:26183686

  12. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

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    Ricardo Costa

    2013-01-01

    Full Text Available Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT scans, magnetic resonance imaging (MRI, and positron emission tomography (PET/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU.

  13. 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

  14. Identification of a single base-pair mutation of TAA (Stop codon) → GAA (Glu) that causes light chain extension in a CHO cell derived IgG1

    Science.gov (United States)

    Zhang, Taylor; Huang, Yungfu; Chamberlain, Scott; Romeo, Tony; Zhu-Shimoni, Judith; Hewitt, Daniel; Zhu, Mary; Katta, Viswanatham; Mauger, Brad; Kao, Yung-Hsiang

    2012-01-01

    We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternative in-frame stop codon, were observed by mass spectra analysis. The abnormal peptide peaks present in tryptic and chymotryptic LC–MS peptide mapping were confirmed by N-terminal sequencing as C-terminal light chain extension peptides. Furthermore, LC-MS/MS of Glu-C peptide mapping confirmed the stop221E mutation, which is consistent with a single base-pair mutation in TAA (stop codon) to GAA (Glu). The light chain variants were approximately 13.6% of wild type light chain as estimated by RP-HPLC analysis. DNA sequencing techniques determined a single base pair stop codon mutation, instead of a stop codon read-through, as the cause of this light chain extension. To our knowledge, the stop codon mutation has not been reported for IgGs expressed in CHO cells. These results demonstrate orthogonal techniques should be implemented to characterize recombinant proteins and select appropriate cell lines for production of therapeutic proteins because modifications could occur at unexpected locations. PMID:23018810

  15. 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.

  16. Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology

    Science.gov (United States)

    Chen, Shuyuan; Ding, Jia-Huan; Bekeredjian, Raffi; Yang, Bing-Zhi; Shohet, Ralph V.; Johnston, Stephen A.; Hohmeier, Hans E.; Newgard, Christopher B.; Grayburn, Paul A.

    2006-05-01

    This study describes a method of gene delivery to pancreatic islets of adult, living animals by ultrasound targeted microbubble destruction (UTMD). The technique involves incorporation of plasmids into the phospholipid shell of gas-filled microbubbles, which are then infused into rats and destroyed within the pancreatic microcirculation with ultrasound. Specific delivery of genes to islet beta cells by UTMD was achieved by using a plasmid containing a rat insulin 1 promoter (RIP), and reporter gene expression was regulated appropriately by glucose in animals that received a RIP-luciferase plasmid. To demonstrate biological efficacy, we used UTMD to deliver RIP-human insulin and RIP-hexokinase I plasmids to islets of adult rats. Delivery of the former plasmid resulted in clear increases in circulating human C-peptide and decreased blood glucose levels, whereas delivery of the latter plasmid resulted in a clear increase in hexokinase I protein expression in islets, increased insulin levels in blood, and decreased circulating glucose levels. We conclude that UTMD allows relatively noninvasive delivery of genes to pancreatic islets with an efficiency sufficient to modulate beta cell function in adult animals. diabetes | gene therapy | ultrasound

  17. 重症儿童高血糖与胰腺β细胞功能障碍的研究%Relationship between hyperglycemia and pancreatic beta cell dysfunction in critically ill children

    Institute of Scientific and Technical Information of China (English)

    刘萍萍; 祝益民; 肖政辉; 张新萍; 仇君; 卢秀兰

    2014-01-01

    Objective To analyse the relationship between insulin resistance and the pancreatic beta cell dysfunction in critically ill children with hyperglycemia,to investigate the relationship between the pancreas injury and pancreatic beta cells dysfunction.Methods Seven hundred and thirty-six critically ill children admitted in PICU of Hunan Children's Hospital from Nov 2012 to Mar 2013 were reviewed and analyzed.According to the maximum intravenous blood glucose within 24 h after admission,they were divided into severely elevated group (blood glucose ≥11.1 mmol/L,n =67),slightly elevated group(blood glucose 6.1 ~ 11.1 mmol/L,n =361) and control group (blood glucose ≤ 6.1 mmo/L,n =308).Serum insulin,C peptide,serum amylase,lipase,urinary amylase,HOMA-β,HOMA-IR were compared among 3 groups.According to the severity of sepsis,they were divided into non-sepsis group (n =414),sepsis group (n =237),severe sepsis group (n =64),septic shock group (n =21).Blood glucose,serum insulin,C peptide,HOMA-βand HOMA-IR were compared among 4 groups.Results (l)The levels of insulin,C peptide,blood amylase,lipase and urine amylase were gradually increased with elevated blood sugar(rs =0.235,P < 0.05;C =0.142,P < 0.05 ; rs =0.142,P < 0.05 ; rs =0.119,P < 0.05 ; r.s =0.093,P < 0.05).The differences among 3 groups were significant (P < 0.05).The levels of serum amylase (IU/L) [102.81 (10.48-191.69)],lipase(U/L) [69.75(10.67-121.85)] were higher than upper limit of normal in severely elevated group.HOMA-β fell to 18.75% in severely elevated group.The level of HOMA-β was decreased with the increase of blood sugar level (rs =-0.108,P < 0.05).The level of HOMA-IR was increased with the elevated blood sugar level(rs =0.455,P < 0.05).(2) The levels of blood glucose,insulin,C peptide and HOMA-β were significantly different among 4 groups of non-sepsis,sepsis,severe sepsis and septic shock group (P < 0.05),HOMA-IR showed no significant difference among 4 groups (P > 0

  18. Clinical Allograft Islets Post-transplant 1 Year for Type 1 Diabetes Mellitus with A Modified Edmonton Protocol%同种异体胰岛细胞移植治疗1型糖尿病的护理

    Institute of Scientific and Technical Information of China (English)

    张雯

    2015-01-01

    目的:总结同种异体胰岛细胞移植治疗1型糖尿病的护理研究。方法按JDRF标准筛选3例1型糖尿病患者(T1DM),并实施同种异体胰岛细胞移植。在GMP实验室内以Liberase 酶消化胰腺器官、COBE 2991细胞分离机分离、连续密度梯度纯化,获取高纯度与高活性的胰岛细胞。培养12h后,检测其达到移植标准,再经皮穿刺肝脏门静脉主干,经门静脉将胰岛细胞匀速移植到肝脏内。术后应用各种护理方法,密切观察病情变化和各种并发症的变化。结果2例完全脱离胰岛素治疗,1例胰岛素用量较术前减少60%以上。术后血糖稳定,C肽、糖化血红蛋白在正常范围,肾功能得以改善,无移植并发症、以及低血糖发作,患者掌握了术后自我管理的方法,总结出了个体化的护理经验。结论患者护理效果满意,初步建立同种异体胰岛细胞移植治疗1型糖尿病一整套护理方法。%Objective To investigate the pancreatic islet cell isolation technology,quality standards,and allograft islet cell transplantation in the treatment of type 1 diabetes safety and effectiveness. Methods According to Juvenile Diabetes Research Foundation (JDRF) standard screening method,three cases of type 1 diabetes (T1DM) were selected as allograft islet cells recipi-ents. Using Liberase enzyme digested pancreatic organs,COBE 2991 cell separator,and discontinuous density gradient purification-to obtained high purity and high activity of islet cells. All these procedures were conducted in our GMP facilities. Cultured after 12h,testing islets reached transplant standards,then performed percutaneous hepatic portal vein trunk of the recipients,islet cells were through the portal vein into the recipient liver site. After islet transplantation,using a modified Edmonton immunosuppressive protocol controlled rejection,and monitored of blood glucose,C peptide and glycate hemoglobin level changes regularly for 1-year followed

  19. Effect on the Akt2 in Skeletal Muscle of Rats with Insulin Resistance Treated by Acupuncture

    Institute of Scientific and Technical Information of China (English)

    张梁; 李梅; 易玮; 许能贵; 孙健; 王臻

    2010-01-01

    Objective: To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods: Twenty-four SD rats were randomly divided into a control group, a model group and an acupuncture group. Fasting plasma glucose (FPG), fasting insulin (FINS), insulin sensitivity index (ISI), C peptide (C-P), as well as Akt2 mRNA expression in skeletal muscle of rats were detected by glucose oxidase method, ELISA and real-time PCR. Results: Compared with the control group, the level of FPG, FINS and C-P increased significantly (P<0.01) while ISI and Akt2 mRNA expression decreased markedly in the model group (P<0.01, P<0.05). In the acupuncture group, the levels of FPG, FINS and C-P were much lower than in the model group (P<0.01, P<0.01,P<0.05) and ISI and Akt2 mRNA expression increased markedly (P<0.01). Conclusion: The mechanism of acupuncture in treating insulin resistance may relate to the up-regulated of the Akt2 mRNA expression and to the improvement of the signal transduction of PI3K pathway.%目的:观察针刺对胰岛素抵抗模型大鼠骨骼肌Akt2 mRNA表达的影响.方法:将24只SD大鼠随机分为空白组、模型组和针刺组,用葡萄糖氧化酶法、ELISA、实时荧光定量PCR等方法,检测比较各组大鼠空腹血糖(Fasting Plasma Glucose,FPG)、血浆胰岛素(Fasting Insulin,FINS)、胰岛素敏感性指数(Insulin Sensitivity Index,ISI)、血清C-肽(C Peptide,C-P)和骨骼肌Akt2 mRNA的表达.结果:模型组大鼠的FPG、FINS、C-P较空白组显著升高(P<0.01),ISI和骨骼肌Akt2 mRNA表达显著降低(P<0./01,P<0.05);针刺组的FPG、FINS、C-P较模型组显著降低(P<0.01,P<0.01,P<0.05),ISI和骨骼肌Akt2 mRNA表达显著升高(P<0.01).结论:针刺治疗胰岛素抵抗的作用机理可能与上调Akt2 mRNA的表达,改善PI3K通路的信号转导有关.

  20. The risk factors of type 2 diabetes associated with renal calculus%2型糖尿病伴发肾结石的危险因素

    Institute of Scientific and Technical Information of China (English)

    刘雪芳; 曾炼坤; 夏碧文

    2014-01-01

    Objective To analyze the clinical features and risk factors of patients with type 2 diabetes (T2DM) and renal calculus.Methods Fasting plasma glucose (FPG),glycosylated hemoglobin (HbA1c),serum insulin,c peptide,uric acid,triglyceride,total cholesterol,low-density cholesterol and insulin resistance index in 60 cases of T2DM with renal calculus and 60 cases of T2DM without renal calculus were measured and statistically analyzed.Results The levels of FPG,HbA1c,serum insulin,c peptide,UA,TC,LDL-C and Homa-IR of T2DM patients with renal calculus were (11.4 ± 5.4)mmol/L,(9.5 ± 2.7)%,(10.5 ± 6.2) mlU/L,(3.5 ± 2.3)nmol/L,(377.1 ± 119.3)mmol/L,(5.6 ± 2.1)mmol/L,(5.5 ± 3.9)mmol/L and (5.1 ± 3.7) respectively,significantly higher than those of T2DM patients without renal calculus (P < 0.05).Conclusions Insulin resistance,hyperglycemia,high uric acid and disorder of lipid metabolism may be risk factors of T2DM associated with renal calculus.%目的 分析2型糖尿病伴发肾结石患者的临床特征,探讨2型糖尿病伴发肾结石的相关危险因素.方法 采用回顾性分析方法,测定2型糖尿病伴肾结石组患者(60例)与2型糖尿病不伴肾结石组患者(60例)的空腹血糖(FPG)、糖化血红蛋白(HbA1c)、血清胰岛素、c肽、尿酸(UA)、甘油三脂(TC)、总胆固醇(TC)、低密度胆固醇(LDL-C)水平,计算胰岛素抵抗指数(Homa-IR),统计分析两组患者上述指标结果差异性.结果 2型糖尿病伴肾结石组患者FPG(11.4±5.4) mmol/L、HbA1c%(9.5±2.7)、空腹血清胰岛素(10.5±6.2)mIU/L、空腹c肽(3.5±2.3) nmol/L、UA(377.1±119.3) mmol/L、TC(5.6±2.1) mmol/L、LDL-C(5.5±3.9)mmol/L、Homa-IR(5.1±3.7),上述指标水平较2型糖尿病不伴肾结石组显著性升高(P值分别为0.035,0.026,0.017,0.004,0.048,0.037,0.022,0.029,均小于0.05).结论 胰岛素抵抗、高血糖、高尿酸、脂代谢紊乱可能是2型糖尿病伴发肾结石的危险因素.