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Sample records for adding insulin glargine

  1. Insulin glargine overdose

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    Fatma Sari Dogan

    2012-01-01

    Full Text Available Insulin glargine is a long acting novel recombinant human insulin analogue indicated to improve glycemic control, in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. The time course of action of insulins including insulin glargine may vary between individuals and/or within the same individual. Insulin glargine is given as a 24-h dosing regimen and has no documented half-life or peak effect. Hypoglycemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. We present a case of a 76-year-old male insulin-dependent diabetic patient with refractory hypoglycemia secondary to an intentional overdose of insulin glargine. We would like to highlight the necessity of prolonging IV glucose infusion, for a much longer period than expected from pharmacokinetic properties of these insulin analogues after intentional massive overdose.

  2. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    Lantus® ... Insulin glargine is used to treat type 1 diabetes (condition in which the body does not produce insulin and ... diabetes. In patients with type 1 diabetes, insulin glargine must be used with another type of insulin ( ...

  3. Le medicament du mois. Insuline glargine (Lantus).

    OpenAIRE

    Scheen, André

    2004-01-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glar...

  4. Clinical Pharmacokinetics and Pharmacodynamics of Insulin Glargine 300 U/mL.

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    Clements, Jennifer N; Threatt, Tiffaney; Ward, Eileen; Shealy, Kayce M

    2016-10-04

    Concentrated insulin analogs have recently been approved and are available for clinical use in the management of diabetes mellitus. One new product is insulin glargine U-300 (Sanofi), a basal concentrated insulin of 300 U/mL. Several studies have been conducted and completed evaluating blood samples for the pharmacokinetics of insulin glargine U-300 and euglycemic clamp procedures for the pharmacodynamics. This concentrated insulin has a low within-day variability and high day-to-day reproducibility, allowing for a more constant and prolonged duration of action, compared with insulin glargine U-100 (100 U/mL). Insulin glargine U-300 is equally effective, when compared with insulin glargine U-100 for glycemic control in patients with type 1 and 2 diabetes mellitus. Insulin glargine U-300 has a similar efficacy profile to insulin glargine U-100 for glycemic control, yet with lower rates of nocturnal and severe hypoglycemia. Insulin glargine U-300 can be considered an acceptable basal insulin for patients with type 1 and 2 diabetes mellitus, and it has a potential role among patients who are naïve to insulin therapy or require titration of basal insulin. Titration of insulin glargine U-300 would result in less volume and a lower risk of hypoglycemia, compared with insulin glargine U-100. This article evaluates and summarizes the pharmacokinetics and pharmacodynamics of insulin glargine U-300, for patients with type 1 or 2 diabetes mellitus, and summarizes its application to clinical practice.

  5. Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus.

    Science.gov (United States)

    Blair, Hannah A; Keating, Gillian M

    2016-03-01

    Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

  6. Insulin glargine 300 U/ml in the management of diabetes: clinical utility and patient perspectives

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    de Galan BE

    2016-10-01

    Full Text Available Bastiaan E de Galan Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Abstract: There is ongoing interest in optimizing basal insulin treatment by developing insulins with a flat pharmacological profile, a long duration of action (typically beyond 24 hours and minimum day-to-day variation. Glargine-300 is a modified form of the long-acting insulin analog glargine in that it has been concentrated at 300 units/mL rather than the conventional 100 units/mL. Glargine-300 has a longer duration of action and a flatter pharmacological profile than original glargine-100. This property allows for more flexibility around the timing of administration, when injected once per day. Open-label studies in patients with diabetes have shown that treatment with glargine-300 achieves comparable glycemic control compared to treatment with glargine-100, albeit with consistently higher insulin requirements. These studies also showed that treatment with glargine-300 was associated with lower risks of nocturnal hypoglycemia in patients with type 2 diabetes, particularly those already on insulin, whereas data are mixed in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. Treatment with glargine-300 did not appear to affect the risk of overall hypoglycemia, whereas studies lacked sufficient power to investigate the effect on the risk of severe hypoglycemia. Future studies need to establish the role of glargine-300 in the treatment of diabetes alongside the other new long-acting insulin analog, insulin degludec, which was recently introduced to the market. Keywords: insulin glargine-300, type 1 diabetes, type 2 diabetes, hypoglycemia, HbA1c, patient-reported outcomes

  7. [INSULIN GLARGINE 300 U/mL (TOUJEO®)].

    Science.gov (United States)

    Scheen, A J

    2016-02-01

    This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring.

  8. In vitro metabolic and mitogenic signaling of insulin glargine and its metabolites.

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    Mark R Sommerfeld

    Full Text Available BACKGROUND: Insulin glargine (Lantus is a long-acting basal insulin analog that demonstrates effective day-long glycemic control and a lower incidence of hypoglycemia than NPH insulin. After subcutaneous injection insulin glargine is partly converted into the two main metabolites M1 ([Gly(A21]insulin and M2 ([Gly(A21,des-Thr(B30]insulin. The aim of this study was to characterize the glargine metabolites in vitro with regard to their insulin receptor (IR and IGF-1 receptor (IGF1R binding and signaling properties as well as their metabolic and mitogenic activities. METHODS: The affinity of human insulin, insulin glargine and its metabolites to the IR isoforms A and B or IGF1R was analyzed in a competitive binding assay using SPA technology. Receptor autophosphorylation activities were studied via In-Cell Western in CHO and MEF cells overexpressing human IR-A and IR-B or IGF1R, respectively. The metabolic response of the insulins was studied as stimulation of lipid synthesis using primary rat adipocytes. Thymidine incorporation in Saos-2 cells was used to characterize the mitogenic activity. CONCLUSIONS: The binding of insulin glargine and its metabolites M1 and M2 to the IR were similar and correlated well with their corresponding autophosphorylation and metabolic activities in vitro. No differences were found towards the two IR isoforms A or B. Insulin glargine showed a higher affinity for IGF1R than insulin, resulting in a lower EC(50 value for autophosphorylation of the receptor and a more potent stimulation of thymidine incorporation in Saos-2 cells. In contrast, the metabolites M1 and M2 were significantly less active in binding to and activation of the IGF1R and their mitogenicity in Saos-2 cells was equal to human insulin. These findings strongly support the idea that insulin glargine metabolites contribute with the same potency as insulin glargine to blood glucose control but lead to significantly reduced growth-promoting activity.

  9. Comparison of insulin glargine and NPH insulin in the treatment of type 2 diabetes: a review of clinical studies.

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    Duckworth, William; Davis, Stephen N

    2007-01-01

    Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving suboptimal glycemic control. A substantial amount of data exists comparing insulin glargine and neutral protamine Hagedorn (NPH) insulin for long-acting basal insulin coverage. The objective of this systematic review was to provide a balanced appraisal of existing clinical evidence and to determine the appropriate step in therapy for insulin glargine or NPH insulin. Relevant English language articles from 1996 to 2005 were identified through searches of the National Center for Biotechnology Information PubMed database. Search terms included neutral protamine Hagedorn, NPH, insulin glargine, insulin therapy, Type 2 diabetes, insulin analogs, HOE901, and HOE-901. Studies were compared regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin A1c (A1C), fasting plasma glucose (FPG), incidence of hypoglycemia, and other safety assessments. Six original multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, ranging in duration from 4 to 52 weeks, met the inclusion criteria. Two additional analyses represented a subanalysis and a study extension. All of the studies compared insulin glargine with NPH insulin given once or twice daily as monotherapy or in conjunction with oral antidiabetic agents in patients with Type 2 diabetes. Based on available evidence, insulin glargine has shown equal clinical efficacy to that of NPH insulin and similar reductions in A1C and is associated with similar or lower FPG levels. Recent studies also have demonstrated that less frequent nocturnal hypoglycemia incidence is associated with insulin glargine compared with NPH insulin. The known pathophysiology of Type 2 diabetes and the need for basal insulin treatment are presented as rationale for comparison of these insulins.

  10. Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy

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    Jacques Lepercq

    2012-01-01

    Full Text Available As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA1c, severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331 or NPH (371 were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

  11. Comparison of the Efficacy and Safety of Insulin Glargine and Insulin Detemir with NPH Insulin in Children and Adolescents with Type 1 Diabetes Mellitus Receiving Intensive Insulin Therapy

    OpenAIRE

    Dündar, Bumin Nuri; Dündar, Nihal; Eren, Erdal

    2010-01-01

    Objective: The purpose of this study was to compare the efficacy and safety of insulin glargine and detemir with NPH insulin in children and adolescents with type 1 diabetes mellitus (DM). Methods: Thirty four children and adolescents with type 1 DM (mean age 12.7 ± 3.4 years, diabetes duration 5.4 ± 3.0 years) were included in the study. All patients had been receiving intensive insulin therapy with insulin aspart and NPH for at least 6 months before switching from NPH to insulin glargine (G...

  12. Modern approach to basal-bolus therapy with glargine and glulisine insulin analoguesin various age groups

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    N N Volevodz

    2013-03-01

    Full Text Available DCCT (Diabetes Control and Complications Trial study established that intensified insulin therapy in multiple daily injections (MDI or continuous insulin infusion (CSII regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus® and glulisine (Apidra® insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

  13. Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Callesen, Nicoline F; Mathiesen, Jonathan Michael; Ringholm, Lene;

    2013-01-01

    .046). No perinatal deaths were observed. One offspring in each group was born with a major congenital malformation. Conclusions: Glycaemic control and pregnancy outcome were comparable in women using insulin detemir or glargine, except for a lower prevalence of large for gestational age infants in women on glargine...

  14. Effect of insulin glargine on glycemic control in adolescents with type 1-diabetes

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    Hassan M. Mona

    2015-06-01

    Conclusion: The present study encourages the use of insulin glargine in the presence of significant hypoglycemia and glucose variability, with close monitoring of diet and weight. Cost effectiveness and effect on HbA1c and quality of life need further longitudinal studies with larger numbers.

  15. rDNA insulin glargine U300 – a critical appraisal

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    Wang F

    2016-12-01

    Full Text Available Fei Wang,1 Stefanie Zassman,1 Philip A Goldberg2 1Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, CT, USA; 2Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA Background: As the first once-daily basal insulin analog, insulin glargine 100 U/mL (Gla‑100; Lantus® rapidly evolved into the most commonly prescribed insulin therapy worldwide. However, this insulin has clinical limitations. The approval of new basal insulin analogs in 2015 has already started to alter the prescribing landscape.Objective: To review the available evidence on the clinical efficacy and safety of a more concentrated insulin glargine (recombinant DNA origin injection 300 U/mL (Gla-300 compared to insulin Gla-100 in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM.Methods: The following electronic databases were searched: PubMed and MEDLINE (using Ovid platform, Scopus, BIOSIS, and Google Scholar through June 2016. Conference proceedings of the American Diabetes Association (2015–2016 were reviewed. We also manually searched reference lists of pertinent reviews and trials.Results: A total of 6 pivotal Phase III randomized controlled trials known as the EDITION series were reviewed. All of these trials (n=3,500 were head-to-head comparisons evaluating the efficacy and tolerability of Gla-300 vs Gla-100 in a diverse population with T1DM and T2DM. These trials were of 6 months duration with a 6-month safety extension phase.Conclusion: Gla-300 was as effective as Gla-100 for improving glycemic control over 6 months in all studies, with a lower risk of nocturnal hypoglycemia significant only in insulin-experienced patients with T2DM. Overall, patients on Gla-300 required 10%–18% more basal insulin, but with less weight gain compared with Gla-100. Keywords: basal insulin, glargine 300 U/mL, glargine 100 U/mL

  16. Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.

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    Yang, Xuefeng; Mei, Shuang; Gu, Haihua; Guo, Huailan; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-06-01

    We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet.

  17. Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

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    Rhian Clissold

    2007-11-01

    Full Text Available Rhian Clissold1, Steve Clissold21Endocrinology Department, Frenchay Hospital, Bristol, UK; 2Content Ed Net Communications S.L., Madrid, SpainIntroduction: Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing.Aims: This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus.Evidence review: Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin.Clinical value: Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable

  18. Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); J.A.M.J.L. Janssen (Joseph); M. Vähätalo (M.); L.J. Hofland (Leo); S.W.J. Lamberts (Steven); H. Yki-Jarvinen (Hannele)

    2012-01-01

    textabstractAims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In

  19. Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

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    Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

    2016-02-01

    Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities.

  20. Evaluation of the cost effectiveness of exenatide versus insulin glargine in patients with sub-optimally controlled Type 2 diabetes in the United Kingdom

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    Tetlow Anthony P

    2008-08-01

    Full Text Available Abstract Objective Exenatide belongs to a new therapeutic class in the treatment of diabetes (incretin mimetics, allowing glucose-dependent glycaemic control in Type 2 diabetes. Randomised controlled trial data suggest that exenatide is as effective as insulin glargine at reducing HbA1c in combination therapy with metformin and sulphonylureas; with reduced weight but higher incidence of adverse gastrointestinal events. The objective of this study is to evaluate the cost effectiveness of exenatide versus insulin glargine using RCT data and a previously published model of Type 2 diabetes disease progression that is based on the United Kingdom Prospective Diabetes Study; the perspective of the health-payer of the United Kingdom National Health Service. Methods The study used a discrete event simulation model designed to forecast the costs and health outcome of a cohort of 1,000 subjects aged over 40 years with sub-optimally-controlled Type 2 diabetes, following initiation of either exenatide, or insulin glargine, in addition to oral hypoglycaemic agents. Sensitivity analysis for a higher treatment discontinuation rate in exenatide patients was applied to the cohort in three different scenarios; (1 either ignored or (2 exenatide-failures excluded or (3 exenatide-failures switched to insulin glargine. Analyses were undertaken to evaluate the price sensitivity of exenatide in terms of relative cost effectiveness. Baseline cohort profiles and effectiveness data were taken from a published randomised controlled trial. Results The relative cost-effectiveness of exenatide and insulin glargine was tested under a variety of conditions, in which insulin glargine was dominant in all cases. Using the most conservative of assumptions, the cost-effectiveness ratio of exenatide vs. insulin glargine at the current UK NHS price was -£29,149/QALY (insulin glargine dominant and thus exenatide is not cost-effective when compared with insulin glargine, at the current

  1. Potential formula for the calculation of starting and incremental insulin glargine doses: ALOHA subanalysis.

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    Takashi Kadowaki

    Full Text Available BACKGROUND: Pragmatic methods for dose optimization are required for the successful basal management in daily clinical practice. To derive a useful formula for calculating recommended glargine doses, we analyzed data from the Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA study, a 24-week observation of Japanese type 2 diabetes patients. METHODOLOGY/PRINCIPAL FINDINGS: The patients who initiated insulin glargine in basal-supported oral therapy (BOT regimen (n = 3506 were analyzed. The correlations between average changes in glargine dose and HbA1c were calculated, and its regression formula was estimated from grouped data categorized by baseline HbA1c levels. Starting doses of the background-subgroup achieving the HbA1c target with a last-observed dose above the average were compared to an assumed optimal starting dose of 0.15 U/kg/day. The difference in regression lines between background-subgroups was examined. A formula for determining the optimal starting and titration doses was thereby derived. The correlation coefficient between changes in dose and HbA1c was -0.9043. The estimated regression line formula was -0.964 × change in HbA1c+2.000. A starting dose of 0.15 U/kg/day was applicable to all background-subgroups except for patients with retinopathy (0.120 U/kg/day and/or with eGFR<60 mL/min/1.73 m(2 (0.114 U/kg/day. Additionally, women (0.135 U/kg/day and patients with sulfonylureas (0.132 U/kg/day received a slightly decreased starting dose. CONCLUSIONS/SIGNIFICANCE: We suggest a simplified and pragmatic dose calculation formula for type 2 diabetes patients starting glargine BOT optimal daily dose at 24 weeks  =  starting dose (0.15×weight + incremental dose (baseline HbA1c - target HbA1c+2. This formula should be further validated using other samples in a prospective follow-up, especially since several patient groups required lower starting doses.

  2. Insulin Detemir Causes Lesser Weight Gain in Comparison to Insulin Glargine: Role on Hypothalamic NPY and Galanin

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    Mohammad Ishraq Zafar

    2014-01-01

    Full Text Available Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY and galanin (GAL. Methods. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression. Results. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake (P<0.05 and less weight gain (P<0.05, but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower (P<0.05 in the DM+DE group. Conclusion. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL.

  3. Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

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    Dippel Franz-Werner

    2011-10-01

    Full Text Available Abstract Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH the long-acting analogue insulin glargine (GLA is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science and DAHTA (Deutsche Agentur für Health Technology Assessment, and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP. Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER. The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI. Conclusions The incremental cost-utility-ratios (ICER show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK is adopted

  4. Comparison between the therapeutic effect of metformin, glimepiride and their combination as an add-on treatment to insulin glargine in uncontrolled patients with type 2 diabetes.

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    Cheol-Young Park

    Full Text Available To compare the commonly prescribed oral anti-diabetic drug (OAD combinations to use as an add-on therapy with insulin glargine in patients with uncontrolled type 2 diabetes despite submaximal doses of OADs.People with inadequately controlled type 2 diabetes (n = 99 were randomly assigned on a 1∶1∶1 basis to receive insulin glargin, with fixed doses of glimepiride, metformin, and glimepiride plus metformin. Outcomes assessed included HbA1c, the changes in fasting glucose levels, body weight, serum lipids values, insulin dose and symptomatic hypoglycemia.After 24 weeks, HbA1C levels improved from (mean ± SD 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol with insulin glargine plus metformin, from 8.4±1.0% to 7.7±1.3% (68.8±10.6 mmol/mol to 61.1±14.4 mmol/mol with insulin glargine plus glimepiride and from 8.7±0.9% to 7.3±0.6% (71.7±9.8 mmol/mol to 56.2±6.7 mmol/mol with insulin glargine plus glimepirde plus metformin. The decrease in HbA1c was more pronounced with insulin glargine plus glimepiride plus metformin than with insulin glargine plus metformin (0.49% [CI, 0.16% to 0.82%]; P = 0.005 (5.10 mmol/mol [CI, 1.64 to 8.61]; P = 0.005 and insulin glargine plus glimepiride (0.59% [CI, 0.13% to 1.05%]; P = 0.012 (5.87 mmol/mol [CI, 1.10 to 10.64]; P = 0.012 (overall P = 0.02. Weight gain and the risk of hypoglycemia of any type did not significantly differ among the treatment groups.The combination therapy of metformin and glimepiride plus glargine insulin resulted in a significant improvement in overall glycemic control as compared with the other combinations.ClinicalTrials.gov, NCT00708578. The approval number of Kangbuk Samsung hospital's institutional review board (IRB: C0825.

  5. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

    Directory of Open Access Journals (Sweden)

    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  6. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    DEFF Research Database (Denmark)

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    .54 (4.48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3.13; 95% CI 2.04-4.22). INTERPRETATION: A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering...

  7. Cost comparison of insulin glargine with insulin detemir in a basal-bolus regime with mealtime insulin aspart in type 2 diabetes in Germany

    Directory of Open Access Journals (Sweden)

    Dippel, Franz-Werner

    2010-01-01

    Full Text Available Objective: To compare the treatment costs of insulin glargine (IG; Lantus® to detemir (ID; Levemir®, both combined with bolus insulin aspart (NovoRapid® in type 2 diabetes (T2D in Germany. Methods: Cost comparison was based on data of a 1-year randomised controlled trial [1]. IG was administered once daily and ID once (57% of patients or twice daily (43% according to treatment response. At the end of the trial, mean daily basal insulin doses were 0.59 U/kg (IG and 0.82 U/kg (ID. Aspart doses were 0.32 U/kg (IG and 0.36 U/kg (ID. Costs were calculated from the German statutory health insurance (SHI perspective using official 2008 prices. Sensitivity analyses were performed to test robustness of the results. Results: Annual basal and bolus insulin costs per patient were € 1,473 (IG and € 1,940 (ID. The cost of lancets and blood glucose test strips were € 1,125 (IG and € 1,286 (ID. Annual costs for needles were € 393 (IG and € 449 (ID. The total annual cost per patient of administering IG was € 2,991 compared with € 3,675 for ID, translating into a 19% annual cost difference of € 684/patient. Base case results were robust to varying assumptions for insulin dose, insulin price, change in weight and proportion of ID once daily administrations. Conclusion: IG and ID basal-bolus regimes have comparative safety and efficacy, based on the Hollander study, IG however may represent a significantly more cost saving option for T2D patients in Germany requiring basal-bolus insulin analogue therapy with potential annual cost savings of € 684/patient compared to ID.

  8. The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

    NARCIS (Netherlands)

    Gordon, J.; McEwan, P.; Sabale, U.; Kartman, B.; Wolffenbuttel, B. H. R.

    2016-01-01

    Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. Methods: The analysis was based on the recent 4B Study, which compar

  9. Treatment of Abnormal Glucose Regulation and Huge Ovarian Cysts with High Dose Insulin Glargine in an Infant with Leprechaunism - Case Report

    Directory of Open Access Journals (Sweden)

    Ayşe Yasemin Çelik

    2010-12-01

    Full Text Available Introduction: Leprechaunism is a rare autosomal recessive disorder caused by mutations in the insulin receptor gene. In this report; we present a 75 days old infant with leprecahunism treated by high dose insulin glargine.Case Report: Yetmiş day old girl was diagnosed as leprechaunism because of the hyperglycemia, ketoacidosis and dysmorphic appearance. Huge cysts with multiple septa were determined in her ovaries. High dose insulin glargine were adjusted to achieve target blood glucose regulation. Huge ovarian cysts resolved by this treatment.Conclusion: Leprechaunism is characterized by intra-uterine and postnatal growth restriction, lipo-atrophy, characteristic facial features, severe acanthosis nigricans, abnormal glucose homeostasis, clitoromegaly and hirsutism. It is usually fatal within the 1st year of life because of diabetic ketoacidosis or recurrent infections. (Journal of Current Pediatrics 2010; 8: 119-22

  10. Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

    2015-01-01

    Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

  11. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

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

    Science.gov (United States)

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

    2016-03-01

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

  13. The Evolution of Insulin Glargine and its Continuing Contribution to Diabetes Care

    OpenAIRE

    Hilgenfeld, Rolf; Seipke, Gerhard; Berchtold, Harald; Owens, David R.

    2014-01-01

    The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insuli...

  14. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial

    Science.gov (United States)

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    Purpose The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. Methods In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c. Results After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was –0.08% (–0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p administration of IDegAsp with the main meal of the day, tailored to the individual patient’s needs. Trial Registration ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext] PMID:27760129

  15. 新诊断T2MD格列吡嗪联合甘精胰岛素强化治疗的研究%Newly Diagnosed Type 2 Diabetes Glipizide and Insulin Aspart Joint Insulin Glargine Intensive Therapy Research

    Institute of Scientific and Technical Information of China (English)

    赵积海; 董效珍; 高静

    2015-01-01

    目的:观察新诊断2型糖尿病患者采用格列吡嗪和门冬胰岛素分别联合甘精胰岛素强化治疗的有效性、安全性及性价比。方法整群选取2013年2月—2014年12月在该院住院治疗的82例T2DM患者随机分为格列吡嗪联合甘精胰岛素(A组)和门冬胰岛素联合甘精胰岛素(B组),治疗两周后复查患者FBG、2 hBG、FC-P、2 hC-P、血糖达标时间、低血糖发生率及药品费用。结果2周后,两组FBG、2 hBG、较治疗前明显下降,FC-P、2 hC-P较治疗前明显升高(P0.05);两组治疗费用A组明显低于B组,差异有统计学意义(P0.05); two groups of treatment cost was lower in group A than in group B, the difference was statistically significant (P<0.01). Conclusion For patients with newly diagnosed T2DM, Glip-izide combined with Glargine insulin intensive treatment, can control blood glucose well, improve the islet beta cell function in patients with T2DM, and the effect of Insulin aspart Insulin glargine quite, but the former costs less, more convenient.

  16. Insulin glargine combined with glimepiride in treatment of elderly patients with diabetes clinical effectiveness evaluation%甘精胰岛素联合格列美脲治疗老年糖尿病临床效果初评

    Institute of Scientific and Technical Information of China (English)

    周英; 吴强

    2015-01-01

    目的:对甘精胰岛素联合格列美脲治疗老年糖尿病临床效果进行评估.方法 :选取我院2013年至2014年收治的90例老年糖尿病患者作为本次研究的对象 ,随机分成观察和对照组各45 例.对照组采用鱼精蛋白锌胰岛素(N P H )联合格列美脲治疗法 ;观察组采用甘精胰岛素联合格列美脲治疗法.结果 :两组患者治疗后各项指标均有所改善.结论 :甘精胰岛素联合格列美脲治疗老年糖尿病有显著效果.%Objective:the clinical effect of diabetes on insulin glargine combined with glimepiride treatment is evaluated .Methods :90 cases of elderly patients with diabetes in our hospital from 2013 to 2014 were as the research object ,randomly divided into observation and control group with 45 cases in each group .Patients in control group were treated with protamine zinc insulin (NPH) combined with glimepiride therapy ;the observation group treated with insulin glargine combined with glimepiride therapy .Results :the two groups of patients after treatment ,the indexes were improved .Conclu-sion:insulin glargine combined with glimepiridein treatment of elderly patients with diabetes have a significant effect .

  17. A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nomoto

    Full Text Available GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy.In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8% with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD, a comprehensive panel of hemodynamic parameters (Task Force Monitor, and serum metabolic markers were assessed before and after the treatment period.A greater reduction (worsening in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%. The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis.UMIN Clinical Trials Registry System as trial ID UMIN000005331.

  18. Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Laura Fernández Landó

    2012-06-01

    Full Text Available La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2 es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25 e insulina glargina basal (GL. Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0% con = 2 medicaciones orales antidiabéticas (MOAs, aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión dos veces/día, o GL (insulina glargina basal una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002, mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012 y niveles de glucemia menores después del desayuno (P = 0.028 y de la cena (P = 0.011, y a las 3 a.m. (P = 0.005 comparada con GL. La glucemia en ayunas (GA y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P Information on starting insulin regimens in specific populations with type 2 diabetes (T2D is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25 and basal insulin glargine (GL in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0% with = 2 oral antihyperglycemic medications (OAMs, were randomized to add LM25 (25% insulin lispro, 75

  19. Insulin aspart insulin glargine combined effect of type 2 diabetes advantage%门冬胰岛素联合甘精胰岛素治疗2型糖尿病的疗效优势

    Institute of Scientific and Technical Information of China (English)

    李超炎; 陈爱民

    2015-01-01

    目的:探讨门冬胰岛素联合甘精胰岛素治疗2型糖尿病的疗效优势。方法选取2012年1月~2014年6月住院的68例2型糖尿病患者,随机分为门冬胰岛素联合甘精胰岛素组(实验组)和胰岛素泵组(对照组),均为34例,两组均接受正规的糖尿病饮食、运动指导及其他教育,生活作息时间及治疗规律。实验组的所有患者均予以门冬胰岛素(早、中、晚餐前,即刻皮下注射,诺和锐)+甘精胰岛素(晚睡前,皮下注射,来得时)治疗;对照组的所有患者均予以胰岛素泵持续皮下注射门冬胰岛素,两组患者均观察每日空腹血糖、3餐餐后2h血糖、晚10时血糖、空腹C肽、空腹淀粉酶、空腹脂肪酶、日血糖波动情况、日胰岛素用量、低血糖例数、体质指数、治疗达标时间及治疗费用。结果各组治疗前后的血糖控制情况、空腹C肽、空腹淀粉酶、空腹脂肪酶这些指标差异均有统计学意义(P<0.05),体质指数差异无统计学意义(P>0.05);两组的日胰岛素用量、日血糖波动情况差异无统计学意义(P>0.05);实验组较对照组的治疗费用低,低血糖例数多(P<0.05),但达标所需时间长(P<0.05)。结论门冬胰岛素联合甘精胰岛素治疗的低血糖发生率高、达标时间长,但费用低,适用于基层医院及经济困难的患者,值得推广。%Objective To explore joint glargine insulin aspart treatment of type 2 diabetes treatment benefit. Methods Select from January 2012 to June 2014 68 hospitalized patients with type 2 diabetes in hospitalized patients were randomly divided into joint glargine insulin aspart group(experimental group)and insulin pump (control group) were 34 cases,two group were to receive formal diabetic diet,exercise instruction and other educational,lifestyle and treatment time rule.All patients in the experimental group were to be insulin

  20. Acarbose insulin glargine combined on treatment of elderly diabetic%甘精胰岛素联合阿卡波糖治疗老年糖尿病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王明岗

    2010-01-01

    目的 探讨甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效.方法 2008年1月至2010年1月门诊或住院诊治的老年2型糖尿病患者246例,随机分为治疗组126例,对照组120例,治疗组采用甘精胰岛素联合阿卡波糖治疗,对照组采用精蛋白锌重组人胰岛素混合注射液治疗;观察两组临床效果及B细胞功能变化.结果 两组血糖达标时间比较,P<0.05有显著差异性;两组胰岛素日用量、低血糖发生率比较,P<0.01有显著差异性;治疗前、后C肽+胰岛素释放试验检测比较P<0.05有显著差异性.结论 甘精胰岛素联合阿卡波糖能达到良好控制血糖,又能减少胰岛素用量,降低低血糖发生率,有效的改善β细胞功能.而且用药依从性良好的治疗老年2型糖尿病方案.%Objective To investigate insulin glargine combined acarbose treatment of senile diabetes therapy. Methods 246 cases type 2 diabetes were treated in out - patient or in hospital from January 2008 to January 2010 who were randomly divided into treatment group( 126 ) and control group (120). Treatment group patients treated with insulin glargine combined acarbose treatment, and control group were treated by Protamine zinc mixed recombinant human insulin injection treatment;To observe clinical effects and β -cell function. Results Comparison of two groups of blood glucose time, P < 0. 05; Two groups of insulin daily dose, the incidence of hypoglycemia,P < 0. 01 ;Treatment before and after the C peptide + insulin release test comparison, P < 0. 05; Conclusion Insulin glargine combined acarbose can achieve good control of blood glucose and reducing insulin dosage, reducing the incidence of low blood sugar, which an improvement of β cell function. It is a good drug compliance and treatment program in elderly type 2 diabetes.

  1. Efficacy Observation of Insulin Glargine Combined with Nateglinide in Treatment of Senile Type 2 Diabetes Mellitus%甘精胰岛素联合那格列奈治疗老年2型糖尿病32例

    Institute of Scientific and Technical Information of China (English)

    宁尚侠; 李桃荣

    2011-01-01

    目的 观察甘精胰岛素联合那格列奈治疗老年2型糖尿病的效果.方法 将64例老年2型糖尿病患者随机均分为甘精胰岛素组(以下简称"甘精组")和预混胰岛素组(以下简称"预混组").甘精组于三餐前10 min口服那格列奈90~180 mg,晚10:00皮下注射甘精胰岛素;预混组于早晚餐前30min注射预混胰岛素.应用强生稳步血糖仪,每日监测两组患者三餐餐后2h血糖以及晚10:00、凌晨3:00、晨8:00指尖血糖,根据血糖值每2~3 d增减胰岛素剂量2~4 U.空腹血糖低于7.0 mmoL/L和餐后2 h血糖低于10.0 mmol/L为血糖达标,观察血糖达标时间、胰岛素用量、低血糖发生次数和发生病例数.以及16周后患者的空腹血糖、餐后2 h血糖、糖化血红蛋白、体重指数,结果 两组患者的血糖控制均达标,血糖达标时间差异无统计学意义;16周后空腹血糖、餐后2 h血糖、糖化血红蛋白比较,组间差异无统计学意义,治疗前后组内差异有统计学意义(P<0.01);甘精组体重指数无明显变化,预混组较治疗前明显增加(P<0.05);甘精组胰岛素日用量和低血糖发生病例数均显著低于预混组(P<0.01).结论 两种治疗方案对控制血糖都有效,但甘精胰岛素联合那格列奈能减少胰岛素的注射次数和日用量.降低低血糖风险,不增加体重指数,患者依从性好.%Objective To observe the effect of insulin glargine combined with nateglinide in the treatment of senile type 2 diabetes mellitus.Methods Sixty-four patients with type 2 diabetes were divided into 2 groups randomly;glargine group (32 cases) and pre-mixed insulin group (32 cases). The glargine group was given oral nateglinide 90- 180 mg at 10 min before breakfast, lunch and supper respectively and hypodermical injection of glargine once at 22 o'clock every night, while the pre -mixed insulin group was hypodermically injected with the pre-mixed insulin at 30 min before breakfast and supper

  2. Drug-use patterns of initially prescribed insulin detemir and insulin glargine in the Netherlands; A comparative analysis using pharmacy data from IADB.nl

    NARCIS (Netherlands)

    Visser, S.T.; Vegter, S.; Boersma, C.; De Grooth, R.; Postma, M.J.

    2010-01-01

    OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to

  3. Observe the use of insulin glargine in diabetic stroke rehabilitation%甘精胰岛素在糖尿病脑卒中康复的应用观察

    Institute of Scientific and Technical Information of China (English)

    李锐莉; 李莲花; 兰倩

    2014-01-01

    目的:观察甘精胰岛素联合口服降糖药物在2型糖尿病脑卒中康复治疗中的疗效。方法将2型糖尿病脑卒中患者80例随机分为试验组和对照组,每组40例,2组均行常规康复治疗。试验组给予入院后胰岛素的强化治疗,7 d~10 d后甘精胰岛素联合一种降糖药物降血糖,对照组给予常规口服药物降血糖。观察2组患者治疗后4周、8周神经功能评分,比较患者康复治疗疗效。结果试验组康复效果优于对照组,尤以治疗后8周效果显著。结论甘精胰岛素在糖尿病脑卒中康复治疗中具有良好作用,值得推广。%Objective Clinical observation of insulin glargine combined with oral hypoglycemic drugsin type2 diabetes, stroke rehabilitation. Methods 80 cases of type 2 diabeticpatients with stroke,randomly divided into experimental group,control group.40 patients in each group,two groups were given conventional rehabilitation therapy. The experimental group received intensive therapy of insulinafter admission ,7-10 days after insulin glargine combined with a hypoglycemic drug reducing blood sugar.The control group was given conventional oral hypoglycemicdrugs. The two groups were observed respectively after treatment 4 weeks,8 weeks,the use of neural function score,compared with the effect of rehabilitation therapy. Results The effect of experimental group is better than the control group. Conclusion insulin glargine have a good effect on stroke rehabilitation in the treatment of diabetes.

  4. Therapeutic effect of glargine insulin combined with acarbose in elderly diabetic patients%甘精胰岛素联合阿卡波糖在老年糖尿病患者中的应用

    Institute of Scientific and Technical Information of China (English)

    罗小勇

    2013-01-01

    Objective To investigate the clinical efficacy and safety of glargine insulin combined with protamine zinc recombinant lispro insulin in elderly diabetic patients.Methods 96 cases of elderly diabetic were divided into the observation group (52 cases) and control group (44 cases),the control group was given protamine zinc recombinant insulin lispro treatment,and therapeutic effect was observed.Results After treatment FEG,2PBG and HbAlc were significantly lower than those before treatment (P<0.05); after treatment,glycemic index showed no significant difference between the two groups (P>0.05); the observation group' s hypoglycemia was 3.64%,significantly lower than 15.91% of the control group (P<0.05).Conclusion The combined therapy of the glargine insulin and acarbose treatment for senile diabetes is secure,effective,and patients are easier to accept.%目的 探讨甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效及安全性.方法 将96例老年糖尿病患者分为观察组52例和对照组44例,观察组给予甘精胰岛素联合阿卡波糖治疗,对照组给予精蛋白锌重组赖脯胰岛素治疗,观察两组患者治疗效果.结果 两组患者治疗后FEG、2PBG及HbAlc均明显低于治疗前(P<0.05);两组患者治疗后各血糖指标比较差异无统计学意义(P>0.05).观察组低血糖发生率为3.64%,明显低于对照组的15.91% (P<0.05).结论 甘精胰岛素联合阿卡波糖治疗老年糖尿病安全、有效,更易被患者接受.

  5. 30 cases of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus curative effect analysis%30例二甲双胍联合甘精胰岛素治疗2型糖尿病疗效分析

    Institute of Scientific and Technical Information of China (English)

    杨丽明

    2012-01-01

    Objective To observe the effect of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus. Methods 30 cases of type 2 diabetes mellitus patients with metformin combined with insulin glargine in the treatment curative effect analysis. Results the fasting plasma glucose and glycosylated hemoglobin decreased significantly, no hypoglycemia, weight index declined. Conclusion metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus patients with medicine, from the good, safe, effective, feasible.%目的观察二甲双胍联合甘精胰岛素治疗2型糖尿病的疗效。方法对30例2型糖尿病患者经二甲双胍联合甘精胰岛素治疗疗效进行临床分析。结果空腹血糖及糖化血红蛋白明显下降,无低血糖发生,体重指数有所下降。结论二甲双胍联合甘精胰岛素治疗2型糖尿病,患者医从性好,安全、有效,具有可行性。

  6. 口服降糖药联合甘精胰岛素及餐前一次门冬胰岛素的治疗达标研究——1+1研究%Efficacy of the addition of a single bolus of insulin glulisine in combination with basal insulin glargine and oral antidiabetic drugs

    Institute of Scientific and Technical Information of China (English)

    天津市"1+1研究"协作组

    2011-01-01

    目的 观察2型糖尿病患者经口服降糖药联合甘精胰岛素治疗仍未达标时,于餐前增加1次门冬胰岛素的有效性、安全性和可行性.方法 采用多中心、开放、自身对照的方法.59例经口服降糖药及甘精胰岛素治疗而糖化血红蛋白(Hb)A1c>6.5%但<9%的患者,于主餐前加用门冬胰岛素治疗16周.结果 16周后,患者HbA1c由治疗前的(8.04±0.58)%降至(6.78±0.30)%(P<0.01),其中13例(22.03%)达到≤6.5%,43例(72.88%)达到<7.0%.早餐前、午餐前及晚餐前注射门冬胰岛素组3餐后血糖均较前明显降低,HbA1c分别为(6.70±0.29)%,(6.80±0.32)%及(6.90±0.21)%.患者低血糖发生率为0.38次/(患者·年),无夜间低血糖和严重低血糖事件发生.患者平均体重及体重指数均明显下降.结论 对于口服降糖药联合甘精胰岛素治疗血糖控制欠佳的2型糖尿病患者,于主餐前增加1次门冬胰岛素可以有效、安全地降低患者血糖,提高达标率,且具有较高可行性.%Objective To investigate the efficacy,safety and feasibility of the addition of a single bolus of insulin glulisine before meal, in combination with basal insulin glargine and oral antidiabetic drugs (OADs) in the treatment of patients with type 2 diabetes. Methods 59 patients with type 2 diabetes who were suboptimally controlled (HbA1c 6.5%-9.0% )on their previous glargine and OADs regimen were included in this 16 weeks, multicentre, open-label and self-control study. A single injection of glulisine was added,at main mealtime,to their existing therapy. Results HbA1c was decreased from (8.04 ±0.58)% to (6.78 ±0.30) % after 16 weeks(P <0.01 ). 13 patients(22.03% ) obtained the target of HbA1c ≤6.5%,43 patients (72.88%)obtained the target of HbA1c <7.0%. Glulisine given at breakfast,lunch or dinner was equally effective in controlling plasma glucose level, and the HbA1c was ( 6.70 ± 0.29 ) %, ( 6.80 ±0.32 ) %, (6.90 ± 0.21 ) % separately. The

  7. Controlled clinical research of poor glycemic control in type 2 diabetes treating with exenatide and insulin glargine%艾塞那肽与甘精胰岛素治疗血糖控制不佳的2型糖尿病的临床对照研究

    Institute of Scientific and Technical Information of China (English)

    杜予俊

    2014-01-01

    Objective To investigate the clinical curative effect,medication compliance and safety of poor gly-cemic control in type 2 diabetes treating with exenatide and insulin glargine. Methods Poor glycemic control patients in our hospital were chose and randomly divided into exenatide group and insulin glargine group,on the basis of the o-riginal oral hypoglycemic drugs treating,respectively gave exenatide and insulin glargine injection to control blood sug-ar,observed and recorded the blood sugar,glycosylated hemoglobin (HbA1c),body weight changes of the two groups before and after treatment, and contrastively analysed the medication adherence and the adverse reactions during the treatment. Results After 26 weeks treatment,the clinical symptoms and blood sugar of the two groups significantly improved than before treatment,the significant efficiency of insulin glargine group was slightly higher than exenatide group,but there was no significant difference (P>0. 05). FBG,2hPG,HbA1c levels of both groups significantly im-proved than before treatment (P0. 05). The weight of exenatide group decreased,the weight of insulin glargine in-creased,but compared with before treatment,the differences had no significance (P>0. 05). The hypoglycemia inci-dence of exenatide group significantly lowered than insulin glargine group (P0. 05 ) . The medication compliance of exenatide group was significantly better than that of insulin glargine group,the difference was significant (P0.05)。两组患者 FBG、2hPG、HbA1c水平均较治疗前有明显改善(P0.05)。艾塞那肽组患者体重呈进行性降低,甘精胰岛素组患者体重呈进行性增加,但与治疗前比较差异均无统计学意义(P>0.05)。艾塞那肽组患者低血糖发生率低于甘精胰岛素组,恶心、腹泻发生率均高于甘精胰岛素组,但差异均无统计学意义(P>0.05)。艾塞那肽组患者用药依从性明显优于甘精胰岛素组,差异有统计学意义(P<0.05)

  8. Effect of insulin glargine on heart and kidney damage in burned rats with delayed fluid resuscitation%甘精胰岛素对延迟复苏烧伤大鼠心脏肾脏损伤的影响

    Institute of Scientific and Technical Information of China (English)

    喻翔; 孔豫苏; 李伟人; 鲁加祥; 李嘉琥

    2015-01-01

    Objective To investigate the protective effect of insulin glargine against heart and kidney damage in burned rats with delayed fluid resuscitation.Methods Twenty-four male Sprague-Dawley ( SD) rats were randomly divided into three groups with 8 rats in each group:sham burn group, burn control group and burn plus insulin group.The sham burn group was immersed into 37 ℃ warm water for 15 seconds to simulate the burn process.The burn control group and burn plus insulin group were immersed into (95 ±0.5)℃ hot water for 15 seconds to make a rat model of 30% total burn surface area ( TBSA) ,Ⅲ degree burn injury rats received an intraperitoneal injection of physiological saline (40 mL/kg) at 6 h after burn.Insulin glargine [1.0 U/(kg· d)] was administered subcutaneously at 2 h postburn in burn plus insulingroup, and subcutaneous injection of the same volume physiological saline in the burn control group.Rats were sacrificed 24 h after burn, abdominal aorta blood was gathered and blood glucose, lactate dehydrogenase ( LDH ), α-hydroxybutyrate dehydrogenase (α-HBDH) , creatine kinase ( CK) , blood urea nitrogen( BUN) , creatinine ( Cr) were analysised.Oxidation and antioxidation parameters in heart and kidney obtained from rats, such as malondialdehyde (MDA), xanthine oxidase (XO), myeloperoxidase (MPO), superoxide dismutase 1 (SOD1), catalase (CAT), glutathion peroxidase (GPx) and the total antioxidant capacity (T-AOC), these parameters were detected by spectrophotometry.Creatine kinase MB ( CK-MB) was determined by immunosuppression.Results (1) Compared with the sham burn group, LDH, α-HBDH, CK, CK-MB, BUN, Cr were significantly higher in the burn control group (P<0.05).In the burn plus insulin group, LDH,α-HBDH, CK, CK-MB, BUN, Cr were significantly lower in comparison with the burn control group (P<0.05).(2) Compared with the sham burn group, the burn control group MDA, XO, MPO in the heart and kidney tissues were significantly higher (P<0.05); SOD1, CAT

  9. Efficacy of insulin glargine combined with repaglinide in treatment of type 2 diabetes mellitus in elders%甘精胰岛素联合瑞格列奈治疗老年2型糖尿病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    宁尚侠

    2011-01-01

    目的 观察老年2型糖尿病(T2DM)病人甘精胰岛素联合瑞格列奈降糖治疗的效果.方法 60例T2DM患者随机分为甘精组和预混组,甘精组三餐前15 min口服瑞格列奈0.5~1.0 mg,晚10∶00皮下注射甘精胰岛素.预混组于早晚饭前30 min注射预混胰岛素,应用罗康全血糖仪,住院期间监测空腹、三餐后2 h、夜10∶00、夜3∶00指尖血糖,根据血糖调整胰岛素剂量.空腹血糖(FPG)0.05),组内与治疗前相比差异有统计学意义(P0.05),甘精组BMI较治疗前无明显增加(P>0.05),预混组BMI较治疗前明显增加(P0.05 ). The duration for reaching the aim was similar in 2 groups ( P >0.05 );and the body mass index ( BMI) was markedly increased in mixed insulin group compared with pre - trial ( P 0.05). The incidence of hypoglycemia in glargine group was significantly lower than that of mixed insulin group ( P <0.01 ). The daily dosage of insulin in glargine group was significantly lower than that of mixed insulin group ( P <0.01 ). Conclusion Both of mixed insulin and insulin glargine combined with repaglinide have visible effects on controlling blood level of glucose, but the latter has better efficacy, better adherence and lower risk of hypoglycemia, it will not increase the body mass index, and it can decrease the frequency of injection and daily dosage of insulin.

  10. Effect of insulin glargine in combination with nateginide on type 2 diabetes%甘精胰岛素联合那格列奈在门诊2型糖尿病中的应用

    Institute of Scientific and Technical Information of China (English)

    胡利东; 栾晓军; 陈劲松

    2011-01-01

    Objective To observe the clinical efficacy of Lantus (insulin glargine)combinaed with nateginide on type 2 diabetes cases. Methods Sixty-eight type 2 diabetes cases meeting the diagnostic criteria of type 2 diabetes were injected with Lantus bedtime and administrated nateginide orally before 3 meals and observed for 12 weeks.. The levels of fasting blood sugar(FBG),glycated hemoglobin(HBALC )and Postprandial Blood Glucose(PBG)were measured before and after treatment,2 hours after treatment. Results 1,2,4,8,12 weeks after treatment,the FBG,PBG,HbAlc were significantly lower than that before treatment (P<0.05)with a low incidence of hypoglycemia. Conclusion The effect of combination of Lantus and nateginide can better simulate the physiological insulin secretion and reduce blood sugar. And the adverse reactions were mild and the patient compliance was good.%目的 观察来得时(甘精胰岛素)与那格列奈联合应用治疗门诊2型糖尿病的临床疗效.方法 选择符合诊断标准的2型糖尿病患者68例,给予睡前注射来得时并三餐前口服那格列奈,观察12周,分别检测治疗前、后空腹血糖(FBG)、餐后2h血糖(PBG)、糖化血红蛋白(HbA1c).结果 治疗后1、2、4、8、12周的FBG、PBG、HbA1c均较治疗前显著降低(P<0.05),低血糖的发生率低.结论 来得时联合应用那格列奈可更好的模拟生理性胰岛素分泌,有效降低血糖,不良反应少,病人依从性好.

  11. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  12. Observation of clinical effect by insulin glargine in the treatment of senile type 2 diabetes mellitus ;patients%甘精胰岛素治疗老年2型糖尿病患者的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    王匀; 黄伟鹏; 梁煜; 郑雯文; 黄海玲; 严志辉

    2015-01-01

    目的:观察老年2型糖尿病患者采用甘精胰岛素治疗的临床效果。方法120例患有2型糖尿病的老年患者,将其随机分为对照组和观察组,每组60例,对照组采用精蛋白锌重组赖脯胰岛素治疗,观察组采用甘精胰岛素治疗。对比两组疗效。结果观察组患者治疗后的低血糖的发生率(13.33%)明显低于对照组(41.67%),观察组患者治疗后餐后2 h的血糖和空腹血糖、血糖达标时间、糖化血红蛋白(HbA1c)水平均好于对照组患者,两组比较差异具有统计学意义(P<0.05)。结论甘精胰岛素治疗老年患者2型糖尿病可缩短患者的血糖达标时间,治疗方案经济、安全、有效,临床价值较高。%Objective To observe the clinical effect of insulin glargine in the treatment of senile type 2 diabetes mellitus patients. Methods A total of 120 senile patients with type 2 diabetes mellitus were randomly divided into control group and observation group, with 60 cases in each group. The control group received insulin protamine zinc restructuring lispro for treatment, and the observation group received insulin glargine for treatment. Curative effects of the two groups were compared. Results The observation group had much lower incidence of hypoglycemia (13.33%) than the control group (41.67%) after treatment. The observation group also had better levels of 2 h postprandial blood glucose, fasting blood-glucose, blood glucose standard time, and glycosylated hemoglobin (HbA1c) than the control group. The differences between the two groups had statistical significance (P<0.05). Conclusion Insulin glargine can shorten blood glucose standard time in treating senile type 2 diabetes mellitus patients, and this method contains high clinical value as economical, safe and effective.

  13. Research on the efficacy and safety of insulin glargine in different administration time for treatment of type 1 diabetes%甘精胰岛素不同给药时间治疗1型糖尿病的疗效及安全性研究

    Institute of Scientific and Technical Information of China (English)

    李颖

    2014-01-01

    目的:探讨不同时间皮下注射甘精胰岛素治疗1型糖尿病的疗效及安全性。方法选取50例1型糖尿病患者,应用门冬胰岛素联合甘精胰岛素进行治疗,在甘精胰岛素不改变用量前提下,给药时间由22:00调整到18:00前后,比较时间调整前后3 d患者空腹血糖( FBG)、早中晚餐后2 h血糖(2hPG)和午餐前血糖的变化情况、门冬胰岛素的用量及午餐前患者低血糖事件发生情况。结果甘精胰岛素调整用药时间后,患者午餐前血糖调整至理想水平,FBG(7.28±2.13)mmol/L比(8.33±2.20)mmol/L、午餐后2hPG下降显著(8.61±2.59)mmol/L 比(9.70±1.75)mmol/L(U=2.425、3.034,均 P<0.05),早餐后2hPG (8.27±2.02)mmol/L比(8.56±2.33)mmol/L和晚餐后2hPG(9.54±1.55)mmol/L比(9.61±1.75)mmol/L变化均不明显(均P>0.05);门冬胰岛素早餐前用量减少,午餐前和晚餐前用量增加;午餐前低血糖事件显著减少(χ2=4.105、5.005,均P<0.05)。结论甘精胰岛素联合门冬胰岛素治疗1型糖尿病患者,在不改变甘精胰岛素用量情况下,给药时间由22:00调整为18:00,可平稳降低空腹血糖,减少午餐前低血糖的发生。%Objective To explore the clinical efficacy and safety of insulin glargine in different administra-tion time for treatment of type 1 diabetes .Methods 50 patients with type 1 diabetes were given insulin aspart and in-sulin glargine treatment scheme , under the premise of not change insulin glargine dosage , delivery time of insulin glargine varied from 22:00 to 18:00,and fasting blood glucose(FBG),2 hours postprandial blood glucose(2hPG), blood glucose and occurrence of hypoglycemia before lunch , amount of insulin aspart were noted and compared between before and after the adjustment .Results After adjustment of insulin glargine′s medication time , patients

  14. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Rosenstock, J; Yki-Järvinen, H;

    2010-01-01

    To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes.......To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes....

  15. 甘精胰岛素联合阿卡波糖治疗老年糖尿病30例及护理分析%Clinical Effect of Insulin Glargine Combined with Acarbose in Treating Senile Diabetes and Nursing Analysis in 30 Cases

    Institute of Scientific and Technical Information of China (English)

    胡明伟; 毛柳

    2015-01-01

    目的:观察甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效。方法选取老年2型糖尿病患者60例,随机均分为治疗组和对照组。治疗前护理人员对所有患者的基本情况进行评估,在整个过程中对其进行健康教育、饮食护理、运动护理、预防低血糖等。治疗组采用甘精胰岛素联合阿卡波糖治疗,甘精胰岛素皮下注射、1次/日,阿卡波糖片口服、3次/日;对照组采用门冬胰岛素30皮下注射,早晚餐前各1次。16周后评价两组疗效。结果治疗组餐后2 h血糖明显高于对照组( P 0.05);治疗组低密度脂蛋白胆固醇低于治疗前水平( P0.05)。结论甘精胰岛素联合阿卡波糖治疗老年糖尿病,能较好控制患者血糖,且低血糖发生率低,依从性好,值得临床推广。%Objective To observe the clinical effect of insulin glargine combined with acarbose in treating senile diabetes and to analyze its nursing. Methods 60 elderly patients with type 2 diabetes mellitus ( T2DM ) were selected and divided into the treatment group and the control group randomly and equally. The nursing staff conducted the evaluation on the basic situation of all patients before treatment and performed the health education, dietary nursing, exercise nursing, hypoglycemia prevention, etc. The treatment group was treated by in-sulin glargine combined with acarbose, insulin glargine by subcutaneous injection once daily, oral acarbose tablets 3 times daily;the con-trol group adopted the Insulin Aspart 30 Injection by subcutaneous injection, once before breakfast and again before dinner. The fasting and postprandial blood glucose level, glycated hemoglobin and incidence of hypoglycemia after 16 weeks were observed and compared between the two groups. The blood pressure and blood lipids in the treatment group were compared between before and after treat-ment. Results The postprandial 2 h blood glucose level in the

  16. Controlled clinical study of the effect of exenatide and insulin glargine for poor glycemic control in type 2 diabetes%艾塞那肽与甘精胰岛素治疗血糖控制不佳2型糖尿病的临床对照研究

    Institute of Scientific and Technical Information of China (English)

    简强; 李德东; 李鹏飞

    2016-01-01

    Objective To investigate the effect of exenatide and insulin glargine for poorly glycemic controlled in type 2 diabetes.Method 92 poor glycemic control patients with type 2 diabetes in the navy general hospital were chosen and divided into exenatide group and insulin glargine group, that each group has 46 cases. The clinical efficiency of the two groups were observed and compared, the changes of the body mass index, glycemic control, and the incidence of associated complications.ResultThe difference of the clinical curative effect between two groups was not statistically significant(P>0.05). Compared two groups’ respective change of their body mass index between before and after treatment, there was no significant difference (P>0.05); the body mass index of exenatide group was lower than the insulin glargine after treatment (P0.05). ConclusionRelative to insulin glargine, exenatide can more effectively reduce body mass index, lower glycated hemoglobin, lower incidence of hypoglycemia, which is worth promoting in clinical practice.%目的:探讨艾塞那肽与甘精胰岛素治疗血糖控制不佳2型糖尿病的临床对照效果。方法选取海军总医院收治的血糖控制不佳2型糖尿病患者92例,按照随机数字表法分为艾塞那肽组和甘精胰岛素组各46例,比较两组患者的各项指标。结果两组患者的临床疗效比较,差异无显著性(P>0.05)。两组患者治疗前的体重指数差异均无显著性(P>0.05)。但治疗后艾塞那肽组体重指数较甘精胰岛素组明显降低(P<0.05)。两组患者治疗后的血糖控制情况均较治疗前有明显好转(P<0.05);甘精胰岛素组的空腹血糖控制水平明显优于艾塞那肽组(P<0.05);艾塞那肽组的餐后2小时血糖、糖化血红蛋白控制水平明显优于甘精胰岛素组(P<0.05);两组患者不良反应发生率比较,差异无显著性(P>0.05)。结论相对甘精胰岛素而言,

  17. 利拉鲁肽和甘精胰岛素治疗2型糖尿病的最小成本分析Δ%Cost-minimization Analysis of Liraglutide and Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    蒙光义; 王冬晓; 庞家莲; 彭评志; 莫金权; 严浩林; 梁慧; 张萍

    2016-01-01

    OBJECTIVE:To evaluate the clinical efficacy of liraglutide and insulin glargine in the treatment of type 2 diabetes mellitus (T2DM) and conduct pharmacoeconomic analysis, and to provide economical and reasonable T2DM treatment plan. METHODS:80 T2DM patients were randomized into liraglutide group and insulin glargine group,with 40 cases in each group. Both groups were given Metformin hydrochloride sustained-release tablet orally 0.5-2.0 g/d,and diabetes mellitus diet and sport training guide after oral antidiabetic drug withdrawal of previous treatment plan. Liraglutide group was given Liraglutide injection hypodermically,0.6-1.2 mg,qd;insulin glargine group was given insulin glargine hypodermically at 22 o’clock,initial dose of 0.2 IU/(kg·d),adjusted according to the levels of PG,FBG,nocturnal blood glucose level till FBG≤7 mmo1/L and 2 h PG ≤10 mmol/L in both group. Treatment course of 2 groups lasted for 12 weeks. The changes of FBG,2 h PG,HbA1c and BMI were ob-served in 2 groups before and after treatment. 2 therapy plans were evaluated and compared by cost-minimization analysis. RE-SULTS:After treatment,the levels of FBG,2 h PG and HbA1c decreased significantly in 2 groups,compared to before treatment, with statistical significance (P0.05). After treat-ment,BMI of liraglutide group decreased significantly compared with before treatment and insulin glargine group,with statistical significance (P0.05). Cost-minimization analysis showed that the cost of insulin glargine group in reducing FBG,2 h PG and HbA1c were less than liraglutide group,but were more than liraglutide group in reducing BMI. Sensitivity analysis demonstrated the stability and reliability of cost-minimization analysis. CONCLUSIONS:Lira-glutide and insulin glargine have the same clinical efficacy,but insulin glargine need lower cost in blood glucose control,and liraglutide is better therapy plan for body weight control.%目的:评价利拉鲁肽和甘精胰岛素治疗2型糖尿病(T2

  18. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  19. 甘精胰岛素联合口服降糖药物对血糖控制不佳的2型糖尿病患者的疗效观察%Efficacy of insulin glargine combined with oral hypoglycemic agent in type 2 diabetic patients with poor glycemic control

    Institute of Scientific and Technical Information of China (English)

    徐迎侠; 刘洪英

    2011-01-01

    Objective To investigate the efficacy and safety of insulin glargine(lantus(R))combined with metformin and pioglitazone in type 2 diabetic patients whose blood glucose levels Were inadequately controlled by oral antidiabetic drugs(OAD).Methods 78 type 2 diabetic patients with poor glycemic control of OAD were randomly divided into group A and B.Patients in group A and B received insulin glargine and NPH insulin respectively in addition to OAD of metformin and pioglitazone.Fasting blood glucose(FBG),2-bour postprandial blood glucose(2 hVG),glycosylated hemoglobin(Hb)A1c and the increase of weight,as well as hypoglycemia rate were abserved after therapy.Results Levels of FBG,2 hPG and HbA1c were lower in group A than those in group B(P0.05).Conclusion The treatment of insulin glargine with metformin and piglitazone in type 2 diabetic patients with poor glycemic control is more efficient.As the basic insulin treatment,glarglne Was more efficient than NPH insulin.%目的 评价甘精胰岛素(来得时(R))与盐酸吡格列酮和二甲双胍联合应用治疗口服降糖药物控制不佳的2型糖尿病患者的有效性和安全性.方法 采用随机法将78例口服降糖药物控制不佳的2型糖尿病患者分为A、B两组.A组为甘精胰岛素(来得时(R))组,B组为精蛋白锌胰岛素(诺和灵N)组,两组均口服吡格列酮和二甲双胍,观察治疗后空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(Hb)A1c水平,以及体重增加值和低血糖发生率.结果 A组FBG、2 hPG及HbA1c水平均低于B组(P均0.05).结论 口服降糖药物疗效差的2型糖尿病患者应用甘精胰岛素联合吡咯列酮和二甲双胍治疗,有更显著的降糖效果;作为基础胰岛素治疗,甘精胰岛素优于精蛋白锌胰岛素.

  20. 甘精胰岛素联合那格列奈治疗老年2型糖尿病疗效观察%Therapeutic effect and safety of nateglinide combined with insulin glargine in treatment of aged patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    郭秋慧

    2009-01-01

    OBJECTIVE To evaluate the comparison of efficacy and safety between nateglinide combined with insulin glargine and mixed protamine zinc recombinant human insulin in treatment of aged patients with type 2 diabetes. METHOOS Fourty aged patients with type 2 diabetes under unsatisfied blood glucose control were randomly divided into 2 groups. 20 patients in the trial group were treated by nateglinide with insulin glargine injection. The other 20 patients in the control group were treated by mixed protamine zinc recombinant human insulin injection. Fasting blood glucose(FBG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin( HbA1C)and hypoglycemia before and after the treatment were observed in two groups. RE-SULTS The levels of FBG,2hPG and HbAIc in trial and control groups after treatment showing significant difference in com-parison with those before treatment. But no significant difference between the two groups(P>0. 05). Hypoglycemia in trial group appeared more frequently than in control group. (P<0. 01 ). CONCLUSION Insulin glargine with Nateglinide can con-trol the blood glucose effectively in aged patients with type 2 diabetes possessing low incidence of hypoglycemia and high safety accompanied by simple and easy way in application.%目的:比较使用甘精胰岛素联合那格列奈与使用预混胰岛素治疗老年2型糖尿病的疗效差异.方法:将40例血糖控制差的老年2型糖尿病患者随机分为甘精胰岛素组和预混胰岛素组.甘精胰岛素组采用甘精胰岛素联合那格列奈治疗,预混胰岛素组采用预混胰岛素2次皮下注射.观察治疗前后2组空腹血糖(FBG)、餐后血糖(2hPG)、糖化血红蛋白(HbA1C),低血糖发生率.结果:2组在空腹血糖、餐后血糖、糖化血红蛋白差异无统计学意义,但甘精胰岛素组在低血糖发生率方面显著低于预混胰岛素组(P<0.01).结论:甘精胰岛素联合那格列奈治疗老年2型糖尿病安全、有效,方法简单易行.

  1. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

    Directory of Open Access Journals (Sweden)

    Yanxing eChen

    2014-05-01

    Full Text Available Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD. Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. Methods: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75U/day for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight. Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and two hours after propofol injection were then investigated by using Western blots and immunohistochemistry.Results: Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase. Conclusion: Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia.

  2. 甘精胰岛素联合二甲双胍治疗血糖控制不佳2型糖尿病的临床价值%Clinical Value of Insulin Glargine Combined with Metformin in the Treat-ment of Type 2 Diabetes with Poorly Controlled Glucose

    Institute of Scientific and Technical Information of China (English)

    李嵘

    2015-01-01

    目的:探讨分析甘精胰岛素联合二甲双胍治疗血糖控制不佳2型糖尿病的临床疗效。方法选取该院2012年12月—2013年12月收治的101例口服降糖药血糖控制不佳的2型糖尿病患者为研究对象,将其依数字表法随机分成两组,观察组55例患者给予甘精胰岛素联合二甲双胍治疗,对照组46例患者给予精蛋白锌胰岛素联合二甲双胍治疗,观察两组临床疗效。结果两组患者空腹血糖(FBG)、餐后2 h血糖(2hPG)及糖化血红蛋白(HbAlc)水平均较治疗前有所改善,观察组改善情况显著优于对照组,差异有统计学意义(P0.05)。结论甘精胰岛素联合二甲双胍治疗血糖控制不佳的2型糖尿病,临床疗效较显著。%Objective To investigate and analyze the clinical efficacy of insulin glargine combined with metformin in the treatment of type 2 diabetes with poorly controlled glucose. Methods One hundred and one type 2 diabetes patients with poorly controlled glucose by oral antidiabetic drug admitted in our hospital from December 2012 to December 2013 were selected as the subjects and randomly divided into two groups in accordance with the digital table method. 55 cases in the observation group were treated by insulin glargine combined with metformin, and 46 cases in the control group were treated by protamine zinc insulin combined with metformin. And the clinical efficacy of the two groups was observed. Results The levels of FBG, 2hPG and HbAlc of the two groups were improved after treatment compared with those before treatment, but the improvement of the observation group was bet-ter than that of the control group, the differences were statistically significant (P0.05). Conclusion The clinical effect of insulin glargine combined with metformin in the treatment of type 2 diabetes with poorly controlled glucose is more significant.

  3. 预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的疗效分析%Analysis of the effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陈云华

    2015-01-01

    目的:探讨预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的临床疗效。方法:将2型糖尿病患者144例随机平分为两组,观察组停用预混胰岛采用甘精胰岛素联合口服降糖药进行治疗,对照组采用预混胰岛素联合口服降糖药进行治疗。观察并比较两组患者FBG(空腹血糖)、HbA1c(糖化血红蛋白)、2 hPG(餐后2 h血糖)及治疗期间患者BMI(体重指数)、低血糖发生次数。结果:两组治疗后FBG、HbA1c、2 hPG等各项指标均下降,下降幅度观察组明显优于对照组;观察组治疗过程中患者BMI无明显变化,而对照组BMI明显上升,且对照组低血糖发生次数明显多于观察组,P<0.05,差异有统计学意义。结论:预混胰岛素治疗效果欠佳的2型糖尿病患者采用甘精胰岛素联合口服降糖药进行治疗,可有效改善患者的FBG、HbA1c水平,降低低血糖风险,且患者体重不会增加。%Objective:To investigate the clinical effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus.Methods:144 patients with type 2 diabetes mellitus were randomly divided into the two groups on average.Patients in the observation group deactivated the premixed insulin therapy,and they were treated by the combination of glargine and oral hypoglycemic agents.Patients in the control group were treated by the combination of premixed insulin and oral hypoglycemic agents.We observed and compared the FBG(fasting blood glucose),HbA1c(glycosylated hemoglobin),2 hPG(2 h postprandial blood sugar)and BMI(body mass index),the number of occurrences of hypoglycemia during treatment.Results:The indicators of FBG,HbA1c,2 hPG were all decreased of the two groups after treatment,and the decline of the observation group was significantly better than the control group.Patients in the observation group had no significant change in BMI

  4. Efficacy and safety of insulin glargine in combination with sitagliptin on elderly patients with type 2 diabetes%甘精胰岛素与西格列汀联用治疗老年2型糖尿病临床观察

    Institute of Scientific and Technical Information of China (English)

    于湛; 田力

    2013-01-01

    Objective To investigate the efficacy and safety of insulin glargine in combination with sitagliptin on elderly patients with type 2 diabetes. Methods 78 patients ( > 60 year-old ) were randomly divided into two groups:insulin glargine/sitagliptin combination group( n =40,group G )and biosynthesis premixed 30/70 insulin group ( n =38,group N ). The dose was adjusted according to blood glucose,the fasting glucose,2 h postprandial blood glucose ,glycosylated hemoglobin( HbA1C ),the incidence of hypoglycemia and body mass index( BMI )after 12 weeks of treatment of the two groups were compared. Results 2 h postprandial blood glucose and the incidence of hypoglycemi-a in group G were less than those in group N( P 0. 05 ). Conclusion The treatment of insulin glargine in combination with sitagliptin is safe, effective and convenient for elderly patients with type 2 diabetes. This treatment program with a small incidence of hypoglycemia is very suitable for old patients with type 2 diabetes complicated with poor cognitive activities inconvenient, poor eyesight or a variety of chronic diseases.%目的 探讨甘精胰岛素联用西格列汀治疗高龄2型糖尿病的疗效及安全性.方法 将78例60岁以上的2型糖尿病患者随机分成甘精胰岛素联用西格列汀组(G组)40例和生物合成预混30/70人胰岛素组(N组)38例,根据血糖情况调整用药剂量,治疗12周后比较两组的空腹血糖、餐后2 h血糖、糖化血红蛋白(HbA1c)、低血糖发生率及体重指数(BMI).结果 G组在空腹2 h血糖和低血糖发生率方面均低于N组,两组比较差异有统计学意义(P<0.05);在餐后血糖、HbA1c和BMI方面两组比较差异无统计学意义(P>0.05).结论 甘精胰岛素与西格列汀联用对老年2型糖尿病患者是一种安全、有效且方便的治疗方案,低血糖发生率低,尤其是对认知力较差、活动不方便、视力差或合并多种慢性病的高龄2型糖尿病患者尤为适用.

  5. 甘精胰岛素与格列美脲联合应用治疗口服降糖药控制不佳2型糖尿病的有效性和安全性%Efficacy and safety of insulin glargine combined with glimepiride in type 2 diabetic patients with poor glycemic control

    Institute of Scientific and Technical Information of China (English)

    吕朝晖; 潘长玉; 陈家伦; 傅祖植; 高妍; 陆菊明; 宁光; 程桦; 高燕明

    2009-01-01

    Objective To investigate the efficacy and safety of insulin glarsine(Lantus~(R))combined with glimepiride(Amaryl~(R))in type 2 diabetic patients whose blood glucose levels were inadequately controlled by oral antidiabetic drugs(OAD).Methods In this open-labeled,randomized,parallel,muhicenter,and non-inferiority study,122 patients were given either once.daily insulin glarsine(n=62)or NPH insulin(n=60)at bedtime,plus glimepiride for 24 weeks.Results Baseline characteristics were similar between the two groups.HbA_(1C) levels were decreased in the insulin glargine and NPH groups over the study period in the per-protocol population (1.38% vs 1.41%).Fasting blood glucose(12.30 to 6.05 mmoL/L and 11.90 to 6.19 mmol/L,respectively)and the mean daily blood glucose(6.28 vs 5.72 mmol/L)decreased similarly in beth groups during the study.Moreover.the number of hypoglycemic episodes was significantly lower in patients with insulin glarsine than those with NPH insulin(46.8% vs 71.1%,P<0.05),being particularly severe(3.2% vs 15.0%,P<0.05)and expressing nocturnal hypoglycemia(37.1% vs 61.7%,P<0.01).Daily insulin dose was increased from 9.7 to 32.5 IU in the insulin glarine group and from 9.8 to 29.5 IU in the NPH insulin group.Conclusion These results confirm earlier reports that insulin glargine provides similar glyeemic control with less hypoglycemia compared with NPH insulin. Insulin glargine yields better results in lowering the incidence of severe and nocturnal hypoglycemia.%目的 评价甘精胰岛素(来得时~(R))与格列美脲(亚莫利~(R))联合应用治疗口服降糖药控制不佳的2型糖尿病的有效性和安全性.方法 采用随机、开放、低精蛋白锌胰岛素注射液(诺和灵N)平行对照和多中心临床研究方法.122例口服降糖药控制不佳的2型糖尿病患者随机分为睡前注射一次甘精胰岛素(n=62)或低精蛋白胰岛素(n=60),清晨口服3mg格列美脲两组,进行为期24周的观察.结果 (1)基线时除甘精胰

  6. 甘精胰岛素联合瑞格列奈在新诊断2型糖尿病中的应用研究%Research on Repaglinide in Insulin Glargine Combined with Newly Diagnosed Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    陈林江

    2012-01-01

    目的 探讨甘精胰岛素联合瑞格列奈治疗新诊断的2型糖尿病的临床疗效,以及对胰岛β细胞功能的影响.方法 选取80例新诊断的2型糖尿病患者,随机分为观察组和对照组各40例,观察组给予瑞格列奈片及甘精胰岛素,对照组给予格列吡嗪片及甘精胰岛素,观察两组患者空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1C),以及应用胰岛素第1时相分泌和稳态模型评价胰岛β细胞功能.结果 观察组患者总有效率95.00%,明显高于对照组的80.00%,二者差异具有统计学意义(P<0.05);治疗6个月后,两组患者FPG、2hPG及HbA1C水平均下降,但观察组下降更明显(P<0.05),并且观察组患者FINS、空腹C肽、AIR 和HOMA-βF优于对照组(P<0.05).观察组患者低血糖发生率为7.50%,低于对照组的30.00%,差异具有统计学意义(P<0.05).结论 甘精胰岛素联合瑞格列奈能有效控制新诊断2型糖尿病患者的血糖,保持和恢复胰岛β细胞功能,低血糖发生率低,安全可靠,值得临床推广应用.%Objective: To investigate the effect of insulin glargine combined with repaglinide in the treatment of newly diagnosed type 2 diabetes, as well as on the function of islet β cell effect. Method: 80 patients with newly diagnosed type 2 diabetic patients, were randomly divided into the observation group and the control group, 40 cases in each group, the groups were observed given repaglinide tablet and insulin glargine, the control group was given glipizide and insulin glargine, two groups were observed in patients with impaired fasting glucose ( FPG ), 2h postprandial plasma glucose ( 2hPG ), glycosylated hemoglobin ( HbA1 C ), as well as the application of first phase insulin secretion and homeostasis model assessment of islet B cell function. Result: In the observation group, the total effective rate was 95% , It was significantly higher than that in control group 80% , the difference was statistically

  7. Clinical Observation of Insulin Glargine Treatment of Elderly Type 2 Diabetic Oral Drugs in Poorly Controlled%甘精胰岛素治疗老年2型糖尿病口服药物控制不佳的临床观察

    Institute of Scientific and Technical Information of China (English)

    冉秀荣; 王晓东

    2012-01-01

      Objective To investigate insulin glargine ( Lantus ) in treating elderly patients with type 2 diabetes mellitus oral drug effect is poor curative effect. Blood glucose, glycosylated hemoglobin were observed before and after treatment, serum lipid, body weight changes, incidence of hypoglycemia in the changes of indexes. Methods 38 cases of elderly patients with type 2 diabetes, in the use of oral drug suboptimal glycemic control (FBG>10.0mmol/L) based on the use of Lantus therapy, follow-up of three months. Results after treatment of patients with blood glucose after meals, bedtime blood glucose, glycosylated hemoglobin were significantly decreased (P10.0mmol/L)的基础上加用来得时治疗,随访3个月.结果治疗后患者三餐前后血糖,睡前血糖、糖化血红蛋白均较治疗前明显下降(P<0.01),体质量变化不大,低血糖发生率低.结论老年2型糖尿病口服药物不达标时,应用来得时,可以有效控制血糖,平稳达标,低血糖发生率低.

  8. 甘精胰岛素联合口服药物治疗2型糖尿病的疗效及安全性分析%Analysis of Efficacy and Safety of the Treatment of Insulin Glargine Combined with Oral Hypoglycemic Drugs for Type 2 Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    李敬华; 刘丽楠; 王素莉; 关树梅; 候雯莉

    2011-01-01

    Objective Evaluation of the efficacy end safety of the treatment insulin glargine combined with OADs for type 2 diabetic patients with poor glycemic control using premixed insulin therapy. Methods 50 cases of type 2 diabetic patients were randomly divided into treatment group (convert premixed insulin into insulin glargine plus OADs) (n= 30) and control group (continue to use the premixed insulin plus OADs) (n= 20), all groups were adjusted the dosage of insulin and OADs based on the levels of blood glucose. After 12 weeks the index of FBG、2hPG、HbA1c、BMI and the incidence of hypoglycemia during the test were compared in two groups. Results Compared with those before treatment, HbA1c、FBG、2hPG of the two groups have declined (P all < 0.01); the treatment group has no significant change in BMI (P >0.05). Compared with the control group, FBG、lunch 2hPG and HbA1c of the treatment group is lower (P all<0.01); BMI of treatment group is lower (P< 0.01); the incidence of hypoglycemia during the test of the treatment group is lower(P< 0.01). Conclusion The treatment of insulin glargine combined OADs for poor glycemic control in type 2 diabetic patients using premixed insulin,can significantly improve the levels of FBG and HbA1c, do not increase body weight, be simple, and can greatly reduce the risk of hypoglycemia.%目的 评价甘精胰岛素联合口服降糖药物(oral hypoglycemic drugs,OADs)治疗方案对使用预混胰岛素血糖控制欠佳的2型糖尿病患者的疗效及安全性.方法 预混胰岛素30/70单独或联合使用OADs血糖控制不良的2型糖尿病患者50例,随机分为治疗组(停用预混胰岛素,改为皮下注射甘精胰岛素联合OADs) (n= 30)和对照组(继续使用预混胰岛素早晚餐前皮下注射联合OADs)(n=20),各组均依据血糖监测水平调整胰岛素及OADs用量.12周后对比两组患者空腹血糖(fasting blood glucose,FBG)、三餐后2h血糖(2-hour postprandial blood glucose,2hPG

  9. 甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响%The effect of insulin glargine combined with carbose on blood glucose attaining standardand pancreatic β cell function of type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    包灵敏; 刘存安

    2013-01-01

    Objective To explore the effect of insulin glargine combined with carbose onblood glucose attaining standard and pancreatic β cell function of type 2 diabetic patients.Methods 70 type 2 diabetic patients were divided into observation group and control group.All the patients got fundamental treatment as diet control and physical exercise.Patients of observing group got extra treatment as using insulin glargine combined with carbose,while patients of control group got extra treatment as using premixed insulin 30R(isophane protamine biosynthetic human insulin),all the treatment lasted for 8 weeks.Results 8 weeks after treatment,the rate of reaching standard of FBG and 2h postprandial plasma glucose and glycosylated hemoglobin (95.0%,85.0% and 77.5%) of observing group were significantly higher than those of control group (77.5%,62.5% and 55.0%) (x2 =5.16,5.23 and 4.53,all P <0.05).The levels of FCP and PCP increased significantly in both groups than that of before treatment (t =2.43,2.32,2.28,2.19,all P < 0.05),and the change of observation group was more obviously than that of control group (t =2.17,2.13,all P < 0.05).The occurrence rate of hypoglycemia of observation group was significantly lower than that of control group(x2 =4.11,P <0.05).Conclusion Treating diabetic patient by insulin glargine combined with acarbose has high safety,and helps to reach the standard of FBG and glycosylated hemoglobin,reduce the incurrence rate of hypoglycemia,protect and improve the function of pancreatic 3 cell,and postpone the beginning and progress of complication.%目的 探讨甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响.方法 选择2型糖尿病患者70例,按就诊病历号顺序随机分为观察组与对照组.两组患者均予以饮食控制和体育锻炼等基础治疗.观察组在此基础上予以甘精胰岛素联合阿卡波糖治疗,对照组在此基础上予以精蛋白生物合成人

  10. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    Directory of Open Access Journals (Sweden)

    Grazia Tundo

    Full Text Available The deposition of β-amyloid (Aβ into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD. Insulin-degrading-enzyme (IDE is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  11. 2型糖尿病从预混胰岛素转换为甘精胰岛素联合口服降糖药物治疗的观察性研究%Study of treatment switching from premixed insulin to glargine combined with oral antidiabetic drugs of patients with type 2 diabetic

    Institute of Scientific and Technical Information of China (English)

    杨艳; 李蓬秋; 包明晶; 刘丽梅; 张学军; 鲜杨; 吴冀川; 张磊; 朱显军

    2014-01-01

    目的 观察2型糖尿病患者从预混胰岛素转换为甘精胰岛素联合口服降糖药物(OADs)治疗的效果、安全性和患者的满意度.方法 采用自身前后对照研究,选择2型糖尿病患者,接受预混胰岛素治疗至少3个月,联合/或未联合OADs治疗,且糖化血红蛋白(HbA1c)≤10.0%的2型糖尿病患者43例,基于患者和医师的考虑,将预混胰岛素转换为甘精胰岛素联合OADs治疗,由医师根据血糖调整胰岛素和OADs的剂量,随访16周,目标空腹血糖≤5.6 mmol/L.结果 共36例患者完成全部随访观察,治疗16周后空腹血糖、餐后2h血糖、HbA1c均与治疗前相当(P均>0.05),而胰岛素用量明显减少[(23.8±6.0)、(9.6±4.0) U/d,t=13.59,P<0.01],体质量指数较治疗前明显下降[(24.4±2.9)、(23.8±2.8)kg/m2,t=3.25,P<0.05];随访期间36例入组患者中15例患者共发生低血糖30次,低血糖发生率41.7%(15/36),均无需他人帮助,少量进食后缓解,无重度低血糖发生,无患者因低血糖反应而退出本研究;36例患者转换前治疗总体满意率为36.1% (13/36),转换后为72.2%(26/36),转换后总体满意度明显高于转换前(x2=6.26,P<O.05).结论 HbA1c≤7.0%时将预混胰岛素转换为甘精胰岛素联合OADs治疗能有效控制血糖,且胰岛素用量及注射次数减少,患者体质量减轻,治疗满意度高.%Objective To evaluation the efficacy,safety and treatment satisfaction of glargine plus oral medications(OADs) switching from premixed insulin on patients with type 2 diabetic.Methods Forty-three patients with type 2 diabetes were enrolled into our study.All patients were treated with twice-daily premixed insulin therapy for at least 3 months with or without OADs and their glycosylated haemoglobin(HbA1c) were less than 10.0%.The aim of OADs treatment was FBG ≤ 5.6 mmol/L Results Thirty-six cases were performed a 16 weeks follow-up and no one lost.After 4 months OADs treatment,the levels of fasting

  12. 糖尿病及长效胰岛素类似物是否增加病人罹患肿瘤的风险?——1例糖尿病合并胰腺癌患者的循证治疗%Does Diabetes and Long-acting Insulin Glargine Increase the Risk of Malignancies: An Evidence-based Treatment for a Diabetic Patient Accompanied with Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    孙倩倩; 王双; 郑玉霞; 廖再波

    2011-01-01

    Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the longacting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present.Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept.2010), MEDLINE (1950 to Sept.2010) and CNKI (2000 to Sept.2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves.Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included.The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves.Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar.It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.%目的 糖尿病与肿瘤的关系以及长效胰岛素类似物是否致癌是目前颇有争议的热点问题,结合1例糖尿病合并胰腺癌患者的病情,用循证临床实践的方法,对糖尿病与肿瘤的关系及长效胰岛素类似物是否致癌进行讨论.方法 计算机检索Cochrane图书馆(2010年第3期)、OVID-EBM Reviews (1991~2010.9),MEDLINE(1950~2010

  13. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

    OpenAIRE

    Werner Haim; Chantelau Ernst A

    2011-01-01

    Abstract In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrie...

  14. Use of an implantable pump for controlled subcutaneous insulin delivery in healthy cats.

    Science.gov (United States)

    Zini, E; Padrutt, I; Macha, K; Riederer, A; Pesaresi, M; Lutz, T A; Reusch, C E

    2017-01-01

    The aim of this study was to examine the safety and reliability of a research-grade implantable pump for controlled delivery of insulin glargine in cats. For this purpose, a small telemetrically controlled drug delivery pump with a refillable reservoir was implanted into the subcutaneous tissues of the dorsal neck in 10 clinically healthy cats. The reservoir was filled with insulin glargine, and the pump was programmed to deliver four boluses of 0.25 IU/kg, 2-3 weeks apart. As a control, insulin glargine (0.25 IU/kg) was injected SC. Blood glucose and plasma insulin glargine concentrations were measured before each bolus and SC injection and for 8 h afterward. Cats were monitored for signs of discomfort. Pumps were easily implanted and well tolerated by all cats. The experiment was completed in five of 10 cats. In four, the pump failed because of technical reasons; another cat developed severe hypoglycaemia attributable to insulin leakage. Overall, plasma insulin glargine increased after six of eight (75%) initial boluses and after one of 16 (6%) successive boluses. Glucose decreased after seven of eight (88%) initial boluses and after four of 16 (25%) successive boluses. Only the first bolus significantly increased plasma insulin glargine (P = 0.008) and decreased glucose (P = 0.008). Of 20 SC injections, 10 (50%) increased plasma insulin glargine (P pump did not cause discomfort in cats, but life-threatening hypoglycaemia occurred in one. Frequent device problems suggest that the pump needs improvements. Because successive boluses did not increase plasma insulin glargine, this type of insulin may not be appropriate with the pump.

  15. Potential value of the Asian Treat to Target Lantus Study (ATLAS) for type 2 diabetes management in China: safety and efficacy of two treatment algorithms using insulin glargine%患者主导与医生主导甘精胰岛素剂量调整:ATLAS中国结果

    Institute of Scientific and Technical Information of China (English)

    潘长玉; 田慧; 李启富; 杨文英; 彭永德; 冯波; 洪天配; 邝建; 杜建玲

    2015-01-01

    Objective The Asian Treat to Target Lantus Study (ATLAS) is designed to compare the effectiveness of a patient-versus physician-led initiation of insulin glargine-based basal management in the specific setting of Asia.This report presents the ATLAS study in China.Methods A total of 161 Chinese patients were randomized to either the patient-led (n =80) titration group or the physician-led (n =81) titration group.In the physician-led group,the patients were asked to be reviewed by a physician every two weeks at outpatient department.In the patient-led group,the patients were empowered to adjust their insulin doses every three days,under strict investigator's supervision,according to the middle value of the last 3 continuous values of FBG.ResultsAfter24 weeks treatment,HbA1C level in each group decreased significantly as compared with baseline and the decreases ranges were similar in the two groups (-1.38% vs-1.21%,P=0.581).A little more patients in the physician-led group (45.7%) achieved blood glucose control (HbA1C < 7%) than those in the patient-led group (43.8%).Severe hypoglycemia was rare in both groups.Body weight did not significantly increase in both groups by 24 weeks.The patients' satisfaction and quality of life were all improved.Conclusion Glargine is safe and effective in improving glycemic control in T2DM patients.A simple patient-led titration algorithm conferred a similar level better glycemic control as compared with physician-led titration,being with no increase in incidence of severe hypoglycemia.Meanwhile,patients' satisfaction and quality of life were improved.%目的 亚洲来得时治疗达标研究(Asian Treat to Target Lantus Study,ATLAS)纳入161例中国2型糖尿病患者,旨在明确患者主导与医生主导甘精胰岛素剂量调整在血糖控制、安全性、生活质量等方面的差异.方法 患者随机分为患者主导和医生主导剂量调整组,医生调整组:患者每2周1次

  16. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  17. Rapid Acting Insulin Use and Persistence among Elderly Type 2 Diabetes Patients Adding RAI to Oral Antidiabetes Drug Regimens

    Science.gov (United States)

    Zhou, Steve; Fan, Tao

    2016-01-01

    We examined the real-world utilization and persistence of rapid acting insulin (RAI) in elderly patients with type 2 diabetes who added RAI to their drug (OAD) regimen. Insulin-naïve patients aged ≥65 years, with ≥1 OAD prescription during the baseline period, who were continuously enrolled in the US Humana Medicare Advantage insurance plan for 18 months and initiated RAI were included. Among patients with ≥2 RAI prescriptions (RAIp), persistence during the 12-month follow-up was assessed. Multivariate logistic regression analyses identified factors affecting RAI use and persistence. Of 3734 patients adding RAI to their OAD regimen, 2334 (62.5%) had a RAIp during follow-up. Factors associated with RAIp included using ≤2 OADs; cognitive impairment, basal insulin use during follow-up; and higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30). Patients were less likely to persist with RAI when on ≤2 OADs versus ≥3 OADs and when having higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30) and more likely to persist when they had cognitive impairment and basal insulin use during follow-up. Real-world persistence of RAI in insulin-naïve elderly patients with type 2 diabetes was very poor when RAI was added to an OAD regimen. PMID:27761472

  18. Glycemic control and long-acting insulin analog utilization in patients with type 2 diabetes

    NARCIS (Netherlands)

    E.M. Heintjes (Edith); T.L. Thomsen (Trine Lyager); F.J.A. Penning-Van Beest (Fernie); T.E. Christensen (Torsten); R.M.C. Herings (Ron)

    2010-01-01

    textabstractIntroduction: The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands. Methods: Insulin-naïve patients with T2D, st

  19. 两种甘精胰岛素治疗糖尿病的疗效及安全性比较:多中心、随机、开放、对照试验%Efficacy and safety of glargine insulin injection Uslen versus Lantus in diabetic patients: a multicenter, randomized, open-labeled controlled trial

    Institute of Scientific and Technical Information of China (English)

    刘云慧; 侯丽琼; 赵铁耘; 田浩明; 吕肖锋; 杨金奎; 李玲; 朱旅云; 张力辉

    2014-01-01

    Objective To evaluate the efficacy and safety of glargine insulin injection (Uslen) in treatment of diabetic patients.Methods A multicenter,randomized,open-labeled and positive control clinical trial included the patients with type 1 or type 2 diabetes mellitus having poor glucose control after using oral antidiabetic drug or short-acting insulin.All patients were treated with Uslen or Lantus for 16 weeks in two groups by a ratio of 1 ∶ 1.The decreased value and qualification rates of glycated hemoglobin A1 c (HbA1 c) and fasting blood glucose (FBG),the incidence of hypoglycemic and the adverse events were compared pretreatment at the end of 16 weeks' treatment.Results All of 664 cases were randomized into two groups and received therapy (1 ∶ 1).But 623 cases were in complete conformity to design plan,313 cases received Uslen therapy and 310 cases received Lantus therapy.There were no different in age,sex,nation,height and weight between two groups.At the end of 16 weeks' treatment,according to the perprotocol analysis (PPS),the decreased values of HbA1c separately (9.2 ± 1.5)% vs (7.7 ± 1.2)% and (9.3±1.5) vs (7.7±1.1)%,FBGseparately (10.2±2.1 vs7.2±2.0) mmol/Land (10.3±2.3 vs 7.4 ± 2.3) mmol/L were all proved significantly in both Uslen group and Lantus group (all P < 0.001).But the changes of HbA1c(1.5% vs 1.6%,F=0.766,P=0.382) and FBG(3.0 vs 2.9 mmol/L,F=0.280,P =0.597) from baseline to endpoint were similar between the treatment groups (P > 0.05).There were no significant difference in the two groups on the qualification rates of HbA1c(26.2% (82/313)vs 21.3% (66/310),P =0.155) and FBG(29.1% (91/313) vs 28.4% (88/310),P >0.05).There were no significant difference separately 22.7% (75/330) and 22.0% (74/333) on hypoglycemia incidences,and the other adverse events incidences were similar separately 0.3% (1/330 vs 1/333,P > 0.05) in two groups.Conclusion Compared with Lantus,the glargine insulin injection of Uslen has

  20. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application.

    Science.gov (United States)

    Owens, D R; Bolli, G B

    2008-10-01

    The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a

  1. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Arpandev Bhattacharyya

    2014-01-01

    Full Text Available Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30 therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A 1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216 switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6% to week 24 (1.0% in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001, while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

  2. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study

    Science.gov (United States)

    Bhattacharyya, Arpandev; Shetty, Raman; Rajkumar, C; Bantwal, Ganapathi

    2014-01-01

    Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort. PMID:25143902

  3. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

    Science.gov (United States)

    Lowndes, Joshua; Sinnett, Stephanie S.; Rippe, James M.

    2015-01-01

    Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old) were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US), one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ± 13.0 vs. 74.5 ± 13.3 kg, p 0.05). There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L), insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L), or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05). These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others. PMID:26512691

  4. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  5. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

    NARCIS (Netherlands)

    Rensing, K.L.; Houttuijn Bloemendaal, F.M.; Weijers, E.M.; Richel, D.J.; Büller, H.R.; Koolwijk, P.; van der Loos, C.M.; Twickler, T.B.; von der Thüsen, J.H.

    2010-01-01

    Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic

  6. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Joshua Lowndes

    2015-10-01

    Full Text Available Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US, one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ±13.0 vs. 74.5 ± 13.3 kg, p < 0.001, but the change in weight was comparable among groups (p > 0.05. There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L, insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L, or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05. These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others.

  7. Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

    Directory of Open Access Journals (Sweden)

    Torres Amelito M

    2011-01-01

    Full Text Available Abstract Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years primarily used vial/syringe (87% and insulin analogs (60%. Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs.

  8. Insulin treatment and breast cancer risk; A systematic review of in vitro, animal and epidemiological evidence

    NARCIS (Netherlands)

    Bronsveld, Heleen K.|info:eu-repo/dai/nl/371740819; Ter Braak, Bas; Karlstad, Øystein; Vestergaard, Peter; Starup-Linde, Jakob; Bazelier, Marloes T.|info:eu-repo/dai/nl/341589802; de Bruin, Marieke|info:eu-repo/dai/nl/270270906; De Boer, Anthonius|info:eu-repo/dai/nl/075097346; Siezen, Christine L.E.; Van De Water, Bob; Van Der Laan, Jan Willem; Schmidt, Marjanka K.

    2015-01-01

    Background: In 2009, the concern has been raised that insulin analogues, especially insulin glargine, might increase risk of (breast) cancer. Many in vitro and epidemiological and some animal studies have been performed, but there is still no clarity on this issue. Objectives: The aim of this study

  9. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  10. Impact of race/ethnicity on efficacy and safety of two starter insulin regimens in patients with type 2 diabetes : A posthoc analysis of the DURABLE trial

    NARCIS (Netherlands)

    Davidson, Jaime A.; Wolffenbuttel, Bruce H.; Arakaki, Richard F.; Caballero, A. Enrique; Jiang, Honghua H.; Hardin, Dana S.

    2013-01-01

    OBJECTIVE: To explore the impact of race/ethnicity on efficacy and safety of twice-daily insulin lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% insulin lispro) and once daily insulin glargine (GL). DESIGN, SETTING, PATIENTS: More than 2,000 Patients with type 2 diabetes enrolled in

  11. Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

    OpenAIRE

    Hartman, Israel

    2008-01-01

    A growing body of medical research has demonstrated that intensive control of serum glucose levels can minimize the development of diabetes-related complications. Success with insulin management ultimately depends on how closely a given regimen can mimic normal physiologic insulin release patterns. The new insulin analogs, including the rapid-acting analogs (aspart, lispro, glulisine), the long-acting basal analogs (glargine, detemir), and the premixed insulin analog formulations (75% neutral...

  12. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  13. 甘精胰岛素治疗1型糖尿病16例临床体会%Glargine for treatment of type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    柴杰

    2009-01-01

    Objective To observe the effect of glargine for treatment of type 1 diabetes. Methods Sixteen type 1 diabetes patients were randomized in two groups. In the Glargine group, 10 patients were given injection Nov-olin R before every meal and injection Glargine at bedtime daily. Meanwhile 6 patients in the NPH group were given injection Novolin R before every meal and injection NPH at bedtime daily. The dosage of insulin was adjusted by blood glucose level, seeking a target of FBG ≤6.5 mmol/L and 2 h PBG≤10.0 mmoL/L. The blood glucose level and incidence of hypoglycemia were observed. Results Mean blood glucose level was similiar in the 2 groups(P > 0.10), but the incidence of hypoglycemia in the Glargine group was significantly lower than that in the NPH group (P < 0.05). Conclusion Glargine initiates the physiological secretion of insulin and controls the blood glucose lev-el more effectively.%目的 比较每日注射一次甘精胰岛素与中性低精蛋白锌人胰岛素(NPH)分别联合3餐前注射短效人胰岛紊(Novolin R)治疗1型糖尿病的疗效.方法 16例1型糖尿病患者(包括儿童l型糖尿病3例,成人迟发自身免疫糖尿病13例)根据用药情况分为2组,甘精胰岛素组10例,每日3餐前注射Novolin R,8例患者每天22:00注射甘精胰岛素,2例患者每天7:00注射甘精胰岛素;对照组6例每日3餐前注射Nov-olin R,22:00注射NPH.根据血糖水平调整胰岛素用量,观察血糖变化和低血糖发生的情况.结果 2组患者治疗后血糖均较治疗前明显下降(P<0.01),2组血糖控制达标所用时间差异有统计学意义(P<0.05).甘精胰岛素组酮体消退时间短于对照组(P<0.05),日用胰岛素剂量低于对照组(P<0.05),血糖平稳下降,血糖波动小,低血糖发生率低于对照组(P<0.05).结论 长效重组甘精胰岛素能模拟人体生理性基础胰岛素分泌,利于1型糖尿病患者的血糖控制,安全性较好.

  14. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

  15. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog

    Directory of Open Access Journals (Sweden)

    Katarina Raslova

    2010-05-01

    Full Text Available Katarina RaslovaMetabolic Center Ltd and Slovak Medical University, Bratislava, Slovak RepublicAbstract: Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements.Keywords: insulin analog, insulin detemir, diabetes mellitus, hypoglycemia, within-subject variability

  16. Patient safety and minimizing risk with insulin administration - role of insulin degludec.

    Science.gov (United States)

    Aye, Myint M; Atkin, Stephen L

    2014-01-01

    Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

  17. Insulin allergy.

    Science.gov (United States)

    Ghazavi, Mohammad K; Johnston, Graham A

    2011-01-01

    Insulin reactions occur rarely but are of tremendous clinical importance. The first was reported in 1922 as a callus reaction at the injection site of insufficiently purified bovine insulin. Porcine insulin was subsequently found to be less allergenic than bovine insulin. Increasingly pure insulins have decreased the risk of adverse reactions, and the production of recombinant insulin with the same amino sequence as human insulin saw a large decrease in adverse reactions. Currently, the prevalence of allergic reactions to insulin products appears to be approximately 2%, and less than one-third of these events have been considered related to the insulin itself. Other reactions occur due to the preservatives added to insulin, including zinc, protamine, and meta-cresol. Allergic reactions can be type I or immunoglobulin E-mediated, type III or Arthus, and type IV or delayed-type hypersensitivity reactions. Type I reactions are the most common and can, rarely, cause anaphylaxis. In contrast, type IV reactions can occur after a delay of several days. Investigations include skin prick testing, patch testing, intradermal testing, and occasionally, skin biopsy.

  18. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

    Directory of Open Access Journals (Sweden)

    Werner Haim

    2011-06-01

    Full Text Available Abstract In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®, insulin aspart ( NovoRapid®, insulin glulisine (Apidra®, and the slow acting analogues insulin glargine (Lantus®, and insulin detemir (Levemir® were gathered from the past 20 years (except for receptor binding studies. A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation. Whether or not these differences have clinical bearings (and among which patient populations remains to be determined.

  19. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years.

    Science.gov (United States)

    Werner, Haim; Chantelau, Ernst A

    2011-01-01

    In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation). Whether or not these differences have clinical bearings (and among which patient populations) remains to be determined.

  20. Pregnancy and the long-acting insulin analogue: a case study.

    Science.gov (United States)

    Caronna, Silvana; Cioni, Federico; Dall'Aglio, Elisabetta; Arsenio, Leone

    2006-04-01

    R.S. is a 22 years old Caucasian woman suffering from obesity, hypertension and Type I Diabetes Mellitus since the age of 6 years. Type I DM treatment includes 3 insulin injections at meal time and one glargine injection at bedtime. The insulin therapy regimen was prolonged during pregnancy and continued after childbirth. Optimal glycemic compensations were monitored throughout the pregnancy using HbA1c variations and other standard controls included in the OBG routine protocols, all within normal values. The pregnancy ended at the 38th week of gestation with a caesarean birth, during which a 3,54 Kg healthy boy with an APGAR of 9 was born. Both the mother and the newborn resulted in perfect health conditions confirming that the possibility of using glargine insulin profiles during pregnancy in selected cases with close monitoring may exist.

  1. Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

    Directory of Open Access Journals (Sweden)

    Chih-Ting Su

    2016-11-01

    Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

  2. Translating structure to clinical properties of an ideal basal insulin.

    Science.gov (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K

    2014-01-01

    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  3. The quest for physiologic insulin replacement.

    Science.gov (United States)

    Owens, David R

    2004-11-01

    Historically, the objective of insulin replacement has been to simulate the 2 major components of insulin secretion in individuals without diabetes mellitus: the low-level basal secretion during the night and periods of fasting, and the prandial secretion in response to food intake. The variable pharmacokinetic and pharmacodynamic characteristics of conventional insulin preparations have made mimicking these physiologic profiles virtually impossible. Balancing the effects of diet, exercise, and the numerous factors contributing to intra- and inter-individual variations in insulin absorption and action, such as type, site of injection, and dosage of insulin, while avoiding the very serious side effect of hypoglycemia in seeking normoglycemia, presents a further challenge. Recently, these limitations have been addressed by recombinant DNA-mediated development of insulin analogues, such as rapid-acting insulin lispro, aspart and glulisine, and the long-acting insulin preparations, insulin glargine and detemir. The molecular structures of these analogues have produced time-action profiles that better approach prandial and basal insulin secretion, thus allowing for easier, safer, and more flexible treatment regimens.

  4. Update on insulin treatment for dogs and cats: insulin dosing pens and more

    Directory of Open Access Journals (Sweden)

    Thompson A

    2015-04-01

    Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

  5. The longitudinal association between glycaemic control and health-related quality of life following insulin therapy optimisation in type 2 diabetes patients. A prospective observational study in secondary care

    DEFF Research Database (Denmark)

    Hajós, Tibor R S; Pouwer, F; de Grooth, R;

    2012-01-01

    ) initiated insulin glargine therapy. Data were collected at baseline, 3 and 6 months, and included HbA(1c) and measures of HRQoL: diabetes symptom distress (Diabetes Symptom Checklist-revised; DSC-r), fear of hypoglycaemia (Hypoglycaemia Fear Survey; HFS-w) and emotional well-being (WHO-5 wellbeing index...

  6. Lantus, the first peakless basal insulin analogue: 10 years of clinical experience in children and adolescents

    OpenAIRE

    Tamara Leonodovna Kuraeva

    2014-01-01

    This review analyses existing literature, including authors' own data, describing the results of clinical trials which assess safety and efficacy of insulin Glargine (Lantus®) in children and adolescents, as well as peculiar features of T1D management in this age group, including the challenge of reducing the rate of hypoglycemia while maintaining adequate glycemic control. The article also discusses various issues in T1D management in children and adolescents, including the role of glycemic ...

  7. Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

    Science.gov (United States)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-05-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

  8. Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

    Directory of Open Access Journals (Sweden)

    Andréia Cristina Conegero Sanches

    2013-09-01

    Full Text Available All patients with Diabetes Mellitus (DM receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%. Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

  9. Patient safety and minimizing risk with insulin administration – role of insulin degludec

    Directory of Open Access Journals (Sweden)

    Aye MM

    2014-04-01

    Full Text Available Myint M Aye,1 Stephen L Atkin21Hull Royal Infirmary, Michael White Diabetes Centre, Hull, UK; 2Weill Cornell Medical College Qatar, Qatar Foundation, Doha, QatarAbstract: Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others

  10. Use of basal insulin and the associated clinical outcomes among elderly nursing home residents with type 2 diabetes mellitus: a retrospective chart review study

    Directory of Open Access Journals (Sweden)

    Davis KL

    2014-10-01

    Full Text Available Keith L Davis,1 Wenhui Wei,2 Juliana L Meyers,1 Brett S Kilpatrick,3 Naushira Pandya4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Sanofi US, Inc, Bridgewater, NJ, USA; 3AnalytiCare, LLC, Glenview, IL, USA; 4Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, FL, USA Background: The management of type 2 diabetes mellitus in long-term care (LTC settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.Methods: This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.Results: A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247 receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.Conclusion: These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies. Keywords: long-term care, nursing homes, type 2 diabetes mellitus, insulin detemir, insulin glargine, NPH insulin

  11. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems

    Directory of Open Access Journals (Sweden)

    Kuhlmann MK

    2014-11-01

    Full Text Available Martin K Kuhlmann,1 Andrea Schmidt2 1Department of Internal Medicine–Nephrology, Klinikum im Friedrichshain, Berlin, Germany; 2Sanofi, Frankfurt, Germany Abstract: More than 380 million people worldwide have diabetes, a disease that accounts for almost US$550 billion in global health care spending. The majority of patients with diabetes will require insulin replacement as part of their therapeutic regimen. In some countries, the approaching patent expiry dates for the long-acting insulin analog insulin glargine mean there is increasing interest in the potential of biosimilar insulins. However, the production and manufacturing of biosimilar insulins is a proprietary, complex, multistep process in which each stage can potentially introduce variability, possibly leading to adverse clinical and safety outcomes. Thus, marketing authorization in countries in which stringent regulatory requirements are in place requires manufacturers to demonstrate similarity in pharmacokinetic/pharmacodynamic properties, clinical efficacy, and adverse event and immunogenicity profiles, as well as provide proof of the quality of the production process between the biosimilar and the reference insulin product. A risk management plan and pharmacovigilance program may also be needed for the approval process. Regulatory guidelines for the introduction of biosimilar insulins differ between countries but are most developed for the European Union. As of the date of submission of this manuscript (April 30, 2014, no insulin or insulin analogs have received marketing authorization based on the European Union standards established for biosimilars; however, European Medicines Agency approval of a biosimilar glargine insulin is awaited for the end of 2014. In recent years several copies of the long-acting insulin glargine have been brought onto the market in countries such as India, the People’s Republic of China, Pakistan, Mexico, and Kenya without following a biosimilar

  12. Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats

    DEFF Research Database (Denmark)

    Nelson, David W; Murali, Sangita G; Liu, Xiaowen

    2008-01-01

    Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted ...

  13. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: A randomized clinical trial

    Science.gov (United States)

    Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. Multicenter (26 pediatric en...

  14. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  15. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, stru...

  16. The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials

    Science.gov (United States)

    Gu, Jianqiu; Meng, Xin; Guo, Yan; Wang, Lei; Zheng, Hongzhi; Liu, Yixuan; Wu, Bingshu; Wang, Difei

    2016-09-01

    Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The meta-analysis was to compare the efficacy and safety of liraglutide added to metformin with other treatments in patients with T2DM. A systematic literature search on PubMed, Embase, Web of Science and the Cochrane library databases were performed. Eligible studies were randomized controlled trials (RCTs) of patients with T2DM who received the combination treatment of liraglutide and metformin. Pooled estimates were performed using a fixed-effects model or random-effects model. A total of nine RCTs met the inclusion criteria. Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP. Moreover, liraglutide combined with metformin did not increase the risk of hypoglycemia, but induced a higher incidence of gastrointestinal disorders. In conclusion, this meta-analysis confirmed the use of liraglutide as add-on to metformin appeared to be effective and safe for patients with T2DM. However, considering the potential limitations in this study, more large-scale, well-conducted RCTs are needed to identify our findings.

  17. A New Choice for Combination Therapy with Insulin:Adding SGLT-2 Inhibitors to Basal Insulin%胰岛素联合治疗的新选择--基础胰岛素+SGLT-2抑制剂

    Institute of Scientific and Technical Information of China (English)

    郭琳; 李强

    2016-01-01

    Mechanism complementary, simple and effective treatment is important for decreasing the blood glucose level of type 2 diabetes patient. Aglycone SGLT2 inhibitors with competitive combined glucose transporters, effectively restrain the activity of renal proximal convoluted tubules SGLT-2, reduce renal tubular epithelial cells reabsorption of glucose, increase the excretion of urine glucose, thereby reducing the blood sugar level. Because the mechanism is not dependent on insulin secretion and insulin action of unique mechanism of action of SGLT2 inhibitor is especially suitable for as a choice for insulin combined treatment drugs. This paper reviews the basic evidence for insulin combined SGLT-2 inhibitor treatment in the following respects:starting time, patients and safety, to point out the combination therapy in the treatment of type 2 diabetes will have good application prospects.%机制互补且简单有效的治疗方案更利于2型糖尿病患者的血糖管理。S G LT-2抑制剂的糖苷配基通过与葡萄糖竞争性结合转运蛋白,有效抑制肾脏近曲小管S G LT-2的活性,减少肾小管上皮细胞对葡萄糖的重吸收,使尿葡萄糖排泄增加,从而降低血糖水平。由于其不依赖于胰岛素分泌和胰岛素作用的独特的作用机制,SGLT-2抑制剂特别适合作为胰岛素联合治疗的选择药物。本文综述了基础胰岛素联合SGLT-2抑制剂治疗的循证证据、起始时机、适应人群和安全性,指出这种联合治疗在2型糖尿病的治疗中将拥有良好的应用前景。

  18. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

    Science.gov (United States)

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2009-01-01

    Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

  19. Effects of metformin on body weight in patients with type 2 diabetes mellitus,receiving insulin analogue treatment

    Directory of Open Access Journals (Sweden)

    T I Romantsova

    2013-03-01

    Full Text Available Aims. To study the dynamics of body weight, waist circumference, blood lipid and insulin demand in patients with type 2 diabetes mellitus (T2DM during first year of combined treatment with metformin and insulin analogues, compared with insulin analogue monotherapy.Materials and Methods. We examined 78 patients with T2DM on newly initiated insulin therapy, including 54 females and 24 males. Median age was 56 [51.0; 64.0] years, median disease duration – 9 [6.8;14.0] years. Participants were subdivided in two groups. First group was comprised of 48 subjects (33 females and 15 males, who received monotherapy with insulin analogues (glargine, de- temir, biphasic Aspart 30 and Humalog Mix 25 or rapid-acting lispro and aspart. Second group included 30 patients (18 females and12 males, who were treated with combined therapy (insulin analogues plus metformin. We measured HbA1c, plasma lipid composition, BMI, waist circumference and insulin demand initially and after one year of follow-up.Results. We showed that combined therapy vs. insulin monotherapy allows better glycemic compensation while reducing insulin demand and lowering risks for weight gain.Conclusions. Combined insulin analogue plus metformin treatment delivers better metabolic control in patients with T2DM and is as- sociated with lower risks for body weight gain and increase in insulin demand against monotherapy with insulin analogues.

  20. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Mearns

    Full Text Available When first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D, the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.A search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks. Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW and systolic blood pressure (SBP, and the risk of developing hypoglycemia, urinary (UTI and genital tract infection (GTI.Sixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide. Glargine, sulfonylureas (SUs and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67. Sodium glucose cotransporter-2 (SGLT2 inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg. SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg. No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03.Adding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive

  1. Early insulin treatment to prevent cardiovascular disease in prediabetes and overt diabetes.

    Science.gov (United States)

    Roman, G; Hancu, N

    2009-02-01

    Type 2 diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD), and CVD represents the leading cause of death in people with type 2 DM. The cardiovascular risk is increased long before diabetes is diagnosed, in the prediabetes stage, when impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) develop. These stages are characterized by dysglycemia, defined as any elevated fasting or postprandial glycemia, extending from the normal range into diabetic range, associated with an increased risk of CVD. Due to metabolic memory demonstrated for type 2 DM as well, early interventions addressed to achieve and maintain glycemic control are required for long-term benefits in terms of both microvascular and macrovascular complications. The recommendation of early insulin therapy in type 2 DM is sustained by its pleiotropic effects, which may be cardioprotective and potentially anti-atherosclerotic. Insulin therapy in prediabetes and earlier in type 2 DM, could be a strategy in preventing cardiovascular disease and type 2 DM progression. To test this hypothesis, a large trial has been designed. Outcome Reduction with an Initial Glargine Intervention trial (ORIGIN) is an international, multicenter, randomized controlled, 2 x 2 factorial trial, investigating the possibility to prevent cardiovascular morbidity and mortality in people with type 2 DM, IGT, and/or IFG, and high cardiovascular risk by treating the normoglycemia with either insulin glargine or omega-3 fatty acid, compared to the standard intervention.

  2. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  3. Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Subhash Kumar Wangnoo

    2015-01-01

    Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

  4. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    Science.gov (United States)

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  5. The role of insulin detemir in overweight type 2 diabetes management

    Directory of Open Access Journals (Sweden)

    Yared N Demssie

    2009-06-01

    Full Text Available Yared N Demssie1, Naveed Younis2, Handrean Soran31Department of Diabetes and Endocrinology, Salford Royal Foundation NHS Trust, Salford, UK; 2Department of Medicine, University Hospital South Manchester Foundation NHS Trust, Wythenshawe, Manchester, UK; 3University Department of Medicine, Central Manchester and Manchester Children’s NHS Foundation Trust, Manchester, UKAbstract: The recent evidence-based shift towards an algorithm of early initiation and aggressive titration of insulin therapy in the management of type 2 diabetes requires the use of an effective insulin formulation that is both safe and acceptable to patients and physicians alike. The advent of the long-acting insulin analogues, insulin detemir and glargine, in the last decade has revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic and pharmacodynamic properties have offered tangible advantage over the conventional intermediate and long-acting insulin preparations in terms of improving glucose control as well as reducing risk of hypoglycemia and weight gain. This review focuses on the pharmacodynamic properties of the long-acting insulin analogue detemir, the outcome of studies on its relative efficacy and safety as well as its proposed place in the management of type 2 diabetes.Keywords: insulin detemir, type 2 diabetes, overweight

  6. Insulin Injection

    Science.gov (United States)

    ... or buttocks. Do not inject insulin into muscles, scars, or moles. Use a different site for each ... you are using insulin.Alcohol may cause a decrease in blood sugar. Ask your doctor about the ...

  7. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  8. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  9. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  10. Lantus, the first peakless basal insulin analogue: 10 years of clinical experience in children and adolescents

    Directory of Open Access Journals (Sweden)

    Tamara Leonodovna Kuraeva

    2014-05-01

    Full Text Available This review analyses existing literature, including authors' own data, describing the results of clinical trials which assess safety and efficacy of insulin Glargine (Lantus® in children and adolescents, as well as peculiar features of T1D management in this age group, including the challenge of reducing the rate of hypoglycemia while maintaining adequate glycemic control. The article also discusses various issues in T1D management in children and adolescents, including the role of glycemic control in development of vascular complications, hypoglycemia and the variability of glycemia. The data confirm the high efficacy of Lantus insulin in respect to metabolic control, including the decrease in the incidence of hypoglycemia and in variability of glycemic profile, the safety of its clinical use in treatment of children, including young children, and adolescents, as well as its ability to improve the quality of life for patients and their parents.

  11. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations.

    Directory of Open Access Journals (Sweden)

    Gerd Luippold

    Full Text Available The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1

  12. Research Progress of Insulin Detemir%地特胰岛素的研究进展

    Institute of Scientific and Technical Information of China (English)

    罗惠辛

    2012-01-01

    地特胰岛素是基础胰岛素类似物,有其独特的分子结构,可与血浆白蛋白可逆性结合,具有长且相对平缓的时间作用曲线,可以显著减少受试者个体内变异性,作用持续时间与甘精胰岛素没有任何差异.众多的临床试验及观察显示地特胰岛素可明显降低糖化血红蛋白、空腹血糖(FPG)、FPG变异性,与甘精胰岛素和中性鱼精蛋白锌胰岛素无明显差异.但在减少低血糖发生和体质量控制方面显示出其优越性.地特胰岛素与胰岛素样生长因子1受体亲和力低,很多研究证实其和人胰岛素相比促生长效应没有变化,但是胰岛素类似物长期应用的安全性尚有争议.%Insulin detemir is one of basal human insulin analogues. It has unique molecule structure, with an acylated fatty acid chain that enables reversible binding to albumin. It has longer and relative flat time action curve,can decrease individual variability significantly,and its duration of action is similar with insulin glargine. Many clinical studies have showed insulin detemir reduced glycosylated hemoglobin, fasting plasma glucose ( FPG )and FPG variability obviously compared with insulin glargine and neutral protamin hagedorn. It showed its advantage in hypoglycaemia event rate and weight gain. Insulin detemir has low affinity with insulin-like growth factor-1 receptor,and is proved,by many studies,no increased or decreased growth promoting effect compared to human insulin, though the safety of long-term insulin analogues treatment is still controversial.

  13. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

    NARCIS (Netherlands)

    Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

    2016-01-01

    BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insu

  14. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...

  15. Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review

    Directory of Open Access Journals (Sweden)

    Wang F

    2012-07-01

    Full Text Available Fei Wang,1 Justine Surh,1 Manmeet Kaur21University of Connecticut School of Pharmacy, Department of Pharmacy Practice, Storrs, 2Joslin Diabetes Center Affiliate, Hospital of Central Connecticut, New Britain, CT, USABackground: Insulin degludec (IDeg is a neutral, ultralong-acting new generation basal insulin analog developed by NovoNordisk currently in Phase III clinical development. IDeg offers a duration of action of more than 42 hours in adults, much longer than current basal insulin formulations.Objective: The aim of this review is to assess the efficacy and safety data of IDeg in the treatment of type 1 and type 2 diabetes mellitus.Methods: Relevant English language articles from 2010 to 2012 were identified through MEDLINE, PubMed, EMBASE, Scopus, BIOSIS, and Google Scholar. Online conference proceedings of the 71st ADA Scientific Sessions and the 47th EASD Annual Meeting were reviewed. Studies were compared in terms of their study designs, primary and secondary efficacy parameters, and tolerability data.Results: There are a total of nine published trials investigating the clinical efficacy and safety of IDeg in over 3000 subjects with type 1 and 2 diabetes. Only three trials were published in full. All were open-label, randomized multicenter trials with durations of 16 to 52 weeks. IDeg and coformulations of IDeg with insulin aspart (IAsp were compared to insulin glargine (IGlar, detemir, and biphasic IAsp 30 (BIAsp 30.Conclusion: Based upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA1c and mean fasting plasma glucose (FPG concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and

  16. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  17. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  18. Diabetes and Insulin

    Science.gov (United States)

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  19. Comparison of the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients

    Institute of Scientific and Technical Information of China (English)

    Gang Wu; Dong-Liang Liu; Xiang-Jun Li; Xiao-Yun Fan

    2016-01-01

    Objective:To investigate the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients.Methods:From May 2014 to June 2015, 128 cases of Type 2 diabetes mellitus were recruited and divided randomly into two groups as observation group and control group. The observation group was given metformin (Glucophage, 0.25 tid) plus basal insulin (glargine) treatment, while the control group was given metformin (Glucophage, initial dose of 0.25 tid; the largest total dose of 2 g) plus other non-euglycemic OADs necessarily for 6 months to adjust dose and control blood glucose at target. The diabetic control indexes, islet function and micro-inflammatory factors were detected and analyzed.Results:After 6 months of medication, the observation group showed significantly lower level of FPG, and HbA1cthan the control group. While AUCc-p, HOMA-β and HOMA-IR of the observation group showed significant difference compared to that of the control group after treatment. Also the micro-inflammatory indexes including hs-CRP, IGF-1, IL-6 and TNF-α of the observation group after treatment were significantly lower than the control group .Conclusions:Type 2 diabetes given metformin plus glargine not only could control and steady blood glucose, but also significant decrease the micro-inflammation state.

  20. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  1. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  2. Clinical comparative study of three kinds of insulin application schemes in the treatment of patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs%三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2型糖尿病临床对比研究

    Institute of Scientific and Technical Information of China (English)

    刘咏梅

    2016-01-01

    Objective:To investigate the clinical effects and safety differences of three kinds of insulin application schemes in the treatment of pa-tients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs including neutral protamine zinc insulin ,insulin glargine and insulin detemir .Methods :150 patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs were chosen in our hospital in the period from March 2012 to June 2015 and randomly divided into 3 groups including A group (50 patients) with neutral protamine zinc insulin ,B group (50 pa-tients) with insulin glargine and C group (50patients) with insulin detemir ;and the blood glucose index level before and after treatment ,insulin dosage and the incidence of hypoglycemia of 3 groups were compared .Results:The blood glucose index level after treatment of 3 groups was significantly lower than before treatment(P0 .05) .The insulin dosage of A group was significantly fewer than B group and C group(P0 .05);A 组患者胰岛素用量显著多于B组、C组 ,差异有统计学意义(P<0 .05);A 组患者低血糖发生率显著高于B组、C组 ,差异有统计学意义(P<0 .05).结论:三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2 型糖尿病临床疗效接近 ,但甘精胰岛素和地特胰岛素应用可有效减少胰岛素用量 ,降低低血糖发生风险.

  3. Adding Ajax

    CERN Document Server

    Powers, Shelley

    2007-01-01

    Ajax can bring many advantages to an existing web application without forcing you to redo the whole thing. This book explains how you can add Ajax to enhance, rather than replace, the way your application works. For instance, if you have a traditional web application based on submitting a form to update a table, you can enhance it by adding the capability to update the table with changes to the form fields, without actually having to submit the form. That's just one example.Adding Ajax is for those of you more interested in extending existing applications than in creating Rich Internet Applica

  4. Mechanisms linking brain insulin resistance to Alzheimer's disease

    OpenAIRE

    Maria Niures P.S. Matioli; Ricardo Nitrini

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dy...

  5. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    Science.gov (United States)

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

  6. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T;

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IR...

  7. Individualized correction of insulin measurement in hemolyzed serum samples.

    Science.gov (United States)

    Wu, Zhi-Qi; Lu, Ju; Chen, Huanhuan; Chen, Wensen; Xu, Hua-Guo

    2016-11-05

    Insulin measurement plays a key role in the investigation of patients with hypoglycemia, subtype classification of diabetes mellitus, insulin resistance, and impaired beta cell function. However, even slight hemolysis can negatively affect insulin measurement due to RBC insulin-degrading enzyme (IDE). Here, we derived and validated an individualized correction equation in an attempt to eliminate the effects of hemolysis on insulin measurement. The effects of hemolysis on insulin measurement were studied by adding lysed self-RBCs to serum. A correction equation was derived, accounting for both percentage and exposure time of hemolysis. The performance of this individualized correction was evaluated in intentionally hemolyzed samples. Insulin concentration decreased with increasing percentage and exposure time of hemolysis. Based on the effects of hemolysis on insulin measurement of 17 donors (baseline insulin concentrations ranged from 156 to 2119 pmol/L), the individualized hemolysis correction equation was derived: INScorr = INSmeas/(0.705lgHbplasma/Hbserum - 0.001Time - 0.612). This equation can revert insulin concentrations of the intentionally hemolyzed samples to values that were statistically not different from the corresponding insulin baseline concentrations (p = 0.1564). Hemolysis could lead to a negative interference on insulin measurement; by individualized hemolysis correction equation for insulin measurement, we can correct and report reliable serum insulin results for a wide range of degrees of sample hemolysis. This correction would increase diagnostic accuracy, reduce inappropriate therapeutic decisions, and improve patient satisfaction with care.

  8. Insulin Human Inhalation

    Science.gov (United States)

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  9. Relationship Between Plasma Insulin Level and Apolipoprotein E Gene Polymorphysm in Alzheimer′s Disease

    Institute of Scientific and Technical Information of China (English)

    Luo Zhuming; Yuan Qiang

    2000-01-01

    Objective: To study relationship between plasma insulin level and apolipoprotein E Gene polymorphysm in Alzheimcr′s Disease. Background: Recent researches have shown that there was a close relationship between ApoE- ε 4 allele and AD. Because of the discovery of hyperinsulineamia in AD patients, the study of insulin on the pathogenesis of AD become a hot point of AD reseearch. Methods: We apply PCR-RFLP to the ApoE genotype study of 45 AD paticnts and 32 normal controls. At the same time, plasma insulin and glucose level was measured in the abovc objects. Results and Discussion: The frequency of ApoE- ε 4 in AD (32.2%) is much higher than in controls (10.9%). On the contrary, the frequency of ApeE- ε 4 is relatively lower in AD than in thc controls. The resistence of hyperinsulineamia in AD. Insulin sensitivity decreased in AD. Conclusion: When gene dose of ApoE- ε 4 increases, the prcvalance of AD increase, while the on-set ages of AD decrease (P<0.05). These findings indicatc that AD patients may have insulin resistance anbd insulin probably play a role in AD pathogenesis. In addition, the s 4 homozygote AD patients seem to have loweer plasma insulin level that the non- ε 4 homozygote AD patients (P<0.05). But this situation need to be replicated in studies of larger sample.

  10. Effect of intrajugular administration of insulin on feed intake, plasma glucose and plasma insulin of sheep.

    Science.gov (United States)

    Deetz, L E; Wangsness, P J

    1980-10-01

    The effect of intrajugular administration of insulin on feed intake, plasma glucose and plasma insulin of 16 wether sheep was studied. A concentrate ration was fed ad libitum to eight wethers, and a forage ration fed to eight different wethers. For each ration, feed intake of four of the eight wethers was measured in one experiment and blood was sampled from the other four wethers at 15, 30, 60 and 120 minutes after injection in a second experiment. The four treatments were saline, 1 mU, 6 mU and 2,000 mU insulin/kg body weight. The highest insulin dose did not affect feed intake of either ration despite producing a marked hypoglycemia, whereas the 6 mU insulin treatment depressed feed intake 1 hour after injection with small changes in concentration of plasma glucose in sheep fed either the concentrate or forage ration. Concentration of plasma insulin was elevated 15 minutes following the 6 mU insulin treatment for the concentrate and forage ration, while 1 mU insulin did not affect plasma insulin. The results of this study suggest a possible role for insulin in the short-term control of feeding in sheep fed either a concentrate or forage ration.

  11. Heat shock response and insulin-associated neurodegeneration

    OpenAIRE

    2011-01-01

    Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN), Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). Despite their prevalence, there are limited therapeutic options available for the treatment of these neurodegenerative disorders. Therefore, establishing a link between insulin/IGF-I and the pathoetiology of these diseases may provide alternative approaches towa...

  12. Endurance training and insulin therapy need to be associated to fully exert their respective beneficial effects on oxidant stress and glycemic regulation in diabetic rats.

    Science.gov (United States)

    Malardé, L; Gratas-Delamarche, A; Le Douairon-Lahaye, S; Zguira, M S; Vincent, S; Lemoine-Morel, S; Groussard, C

    2014-04-01

    In type 1 diabetic subjects, hyperglycemia-induced oxidant stress (OS) plays a central role in the onset and development of diabetes complications. This study aimed to assess the benefits of an endurance training program and insulin therapy, alone or in combination, on the glycemic regulation, markers for OS, and antioxidant system in diabetic rats. Forty male Wistar rats were divided into diabetic (D), insulin-treated diabetic (D-Ins), diabetic trained (D-Tr), or insulin-treated diabetic trained (D-Ins+ Tr) groups. An additional healthy group served as control group. Insulin therapy (Lantus, insulin glargine, Sanofi) and endurance training (a treadmill run of 60 min/day, 25 m/min, 5 days/week) were initiated 1 week after streptozotocin-induced diabetes (45 mg/kg) and lasted for 8 weeks. At the end of the protocol, blood glucose and fructosamine levels, markers for skeletal muscle OS (CML, isoprostanes, GSH/GSSG) and antioxidant system (SOD and GPx activity, ORAC) were assessed. In diabetic rats, the glycemic control was altered and OS marker levels were increased, while the antioxidant system activity remained unchanged. Insulin treatment improved the glycemic regulation, the pro-antioxidant status, and contributed to the reduction of OS marker levels. Endurance training decreased OS marker levels without improving the antioxidant enzyme activity. Endurance training and insulin therapy acted independently (by different ways), but their association prolonged the insulin action and allowed a better adaptation of the antioxidant system. To conclude, our results demonstrate that combination of insulin treatment and endurance training leads to greater benefits on the glycemic regulation and oxidant status.

  13. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  14. String Theory on AdS Spaces

    NARCIS (Netherlands)

    de Boer, J.

    2000-01-01

    In these notes we discuss various aspects of string theory in AdS spaces. We briefly review the formulation in terms of Green-Schwarz, NSR, and Berkovits variables, as well as the construction of exact conformal field theories with AdS backgrounds. Based on lectures given at the Kyoto YITP Workshop

  15. Online Ad Assignment with an Ad Exchange

    OpenAIRE

    Dvořák, Wolfgang; Henzinger, Monika

    2016-01-01

    Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whe...

  16. Antihyperglycemic effect of glargine injection in rat model of type 1 diabetes%甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用

    Institute of Scientific and Technical Information of China (English)

    宋紫辉; 张慧霞; 项宗尚; 范明源; 蔡永明; 张宗鹏

    2016-01-01

    目的 采用链脲佐菌素(streptozotocin,STZ)诱导的大鼠1型糖尿病(insulin-dependent diabetes mellitus,IDDM)模型,评价甘精胰岛素注射液的降血糖作用.方法 健康雄性SD大鼠,单次尾静脉注射2%(质量分数)STZ 58 mg/kg制备IDDM模型,采用随机数字表法将造模成功的动物(禁食血糖≥16.7 mmol/L)分为供试品甘精胰岛素注射液(glargine injection)低、中和高3个剂量组、参照药来得时(Lantus)中剂量组和模型对照组,每组15只;同时设正常对照组.各组动物分别皮下注射甘精胰岛素、来得时或等体积的溶媒,每天给药,连续给药9周.每周定时检测大鼠随机血糖、体质量、摄食量和饮水量;给药结束后,采用全自动生化分析仪检测血清中尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、总胆固醇(total cholesterol,TC)和三酰甘油(triglyceride,TG);采用比色法定量检测糖化血红蛋白(glycosylated hemoglobin,GHb).结果 与模型对照组相比,甘精胰岛素注射液各剂量组大鼠:①体质量增加、摄食量减少;②给药后lh血糖开始降低,2h降至最低,8h基本恢复到给药前,且具有剂量依赖性;③GHb不同程度地降低,具有明显的剂量-效应关系;④血清中BUN和TG降低.结论 在4~8 IU/kg剂量范围内,每日皮下注射2次甘精胰岛素注射液,明显改善IDDM模型大鼠的高血糖症状,其作用效果与来得时相当;连续给药9周后,模型大鼠的血清BUN、TG和GHb显著降低,提示其具有保护肾功能、调节血脂的作用,并能减少糖尿病合并症的发生.

  17. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    Science.gov (United States)

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

  18. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingol

  19. Polarised black holes in AdS

    Science.gov (United States)

    Costa, Miguel S.; Greenspan, Lauren; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{R}}}t. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic AdS behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an AdS soliton that includes the full backreaction of the electric field on the AdS geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both AdS soliton and black hole phases. The corresponding phase diagram generalizes the Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  20. Segmented Strings in $AdS_3$

    CERN Document Server

    Callebaut, Nele; Samberg, Andreas; Toldo, Chiara

    2015-01-01

    We study segmented strings in flat space and in $AdS_3$. In flat space, these well known classical motions describe strings which at any instant of time are piecewise linear. In $AdS_3$, the worldsheet is composed of faces each of which is a region bounded by null geodesics in an $AdS_2$ subspace of $AdS_3$. The time evolution can be described by specifying the null geodesic motion of kinks in the string at which two segments are joined. The outcome of collisions of kinks on the worldsheet can be worked out essentially using considerations of causality. We study several examples of closed segmented strings in $AdS_3$ and find an unexpected quasi-periodic behavior. We also work out a WKB analysis of quantum states of yo-yo strings in $AdS_3$ and find a logarithmic term reminiscent of the logarithmic twist of string states on the leading Regge trajectory.

  1. Insulin resistance: an emerging link in Alzheimer's disease.

    Science.gov (United States)

    Medhi, Bikash; Chakrabarty, Mrinmoy

    2013-10-01

    Relentless progression of Alzheimer's disease (AD) poses a grave situation for the biomedical community to tackle. Agents starting as hot favorites in clinical trials have failed in later stages and it is time we reconsidered our approaches to intervene the disease. Quite some interesting work in the last decade has introduced a new school of thought which factors in neuronal glycemic imbalance as a major component for the development of AD. Insulin resistance in the brain has brought forward subsequent sequelae which might work towards amyloid accretion and/or tau hyperphosphorylation. It is also pointed out that insulin works by distributing iron to neuronal tissue and an insulin resistant state throws it off gear leading to iron overloading of neurons which is ultimately detrimental. A relatively recent investigation finds the role of c-Jun-N-terminal kinase (JNK3) in AD which also seems to bear a link with insulin resistance.

  2. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  3. Growth hormone stimulation of serum insulin concentration in cattle: nutritional dependency and potential mechanisms.

    Science.gov (United States)

    Feng, J; Gu, Z; Wu, M; Gwazdauskas, F C; Jiang, H

    2009-08-01

    Previous studies on the effect of growth hormone (GH) on serum insulin concentration in cattle had generated seemingly conflicting results, and little was known about the mechanism by which GH affects serum insulin concentration in cattle, if it does. In this study, we determined whether the effect of GH on serum insulin concentration in cattle could be affected by the nutritional levels of the animal and whether GH increased serum insulin concentration in cattle by directly stimulating insulin release or insulin gene expression in the pancreatic islets. Administration of recombinant bovine GH increased serum insulin concentration in nonlactating, nonpregnant beef cows fed a daily concentrate meal in addition to ad libitum hay, but it had no effect in those cows fed hay only. Both GH treatments for 1 and 24h increased insulin concentrations in cultures of pancreatic islets isolated from growing cattle. Growth hormone treatment for 24h increased insulin mRNA expression in cultured bovine pancreatic islets. Growth hormone treatment for 16h increased reporter gene expression directed by a approximately 1,500-bp bovine insulin gene promoter in a rat insulin-producing beta cell line. Taken together, these results suggest that exogenous GH can increase serum insulin concentration in cattle, but this effect depends on the nutritional levels of fed cattle, and that GH increases serum insulin concentration in cattle by stimulating both insulin release and insulin gene expression in the pancreatic islets.

  4. Magnetite nanoparticle interactions with insulin amyloid fibrils

    Science.gov (United States)

    Chen, Yun-Wen; Chang, Chiung-Wen; Hung, Huey-Shan; Kung, Mei-Lang; Yeh, Bi-Wen; Hsieh, Shuchen

    2016-10-01

    Accumulation of amyloid fibrils is one of the likely key factors leading to the development of Alzheimer’s disease and other amyloidosis associated diseases. Magnetic nanoparticles (NPs) have been developed as promising medical materials for many medical applications. In this study, we have explored the effects of Fe3O4 NPs on the fibrillogenesis process of insulin fibrils. When Fe3O4 NPs were co-incubated with insulin, Fe3O4 NPs had no effect on the structural transformation into amyloid-like fibrils but had higher affinity toward insulin fibrils. We demonstrated that the zeta potential of insulin fibrils and Fe3O4 NPs were both positive, suggesting the binding forces between Fe3O4 NPs and insulin fibrils were van der Waals forces but not surface charge. Moreover, a different amount of Fe3O4 NPs added had no effect on secondary structural changes of insulin fibrils. These results propose the potential use of Fe3O4 NPs as therapeutic agents against diseases related to protein aggregation or contrast agents for magnetic resonance imaging.

  5. Análogos de insulina: relevancia clínica y perspectivas futuras The clinical relevance of insulin analogues and future perspectives

    Directory of Open Access Journals (Sweden)

    Jhon Jairo BejaranoRoncancio

    2012-12-01

    Full Text Available Desde la década de los noventa han sido diseñados análogos de insulina para el manejo de pacientes diabéticos usando técnicas de ADN recombinante. Las modificaciones de la molécula original de insulina humana les confieren una rápida, ultrarrápida y prolongada acción. Entre las insulinas ultra rápidas están la Aspártica, la Lispro y la Glulisina y entre las de acción prolongada están la Glargina y la Detemir. También se encuentran mezcladas con insulina humana NPH en diferentes proporciones. Aunque existen diferentes tipos de algoritmos terapéuticos, la insulinización sigue siendo una terapia artesanal basada en la experiencia del especialista tratante. La introducción de los análogos de insulina hace más factible el empleo de bolos correctores o dosis extra de insulina para reducir las hipoglicemias puntuales en cualquier momento del día y facilitar el manejo de los carbohidratos en la dieta.Insulin analogues have been engineered through recombinant DNA techniques for managing diabetic patients since the 1990s; modifications to the original human insulin molecule have made them rapid, ultrarapid and prolonged acting. Aspart, lispro and glulisine are ultrafast insulins and glargine and detemir are longacting ones. Such insulins may be premixed in formulations combining neutral protamine Hagedorn (NPH with regular human insulin (70%/30%. Different types of therapeutic algorithms are available nowadays but insulinisation remains a crafted therapy based on the treating specialist's experience. The introduction of insulin analogues enables using correction boluses or extra doses of insulin to reduce hypoglycaemia at any time of the day and facilitates handling carbohydrates in a particular patient's diet.

  6. Clinical Glargine Joint Compound Hyperthyroidism Tablet to Treat Diabetes With Hyperthyroidism%甘精胰岛素联合复方甲亢片治疗糖尿病伴甲亢的临床观察

    Institute of Scientific and Technical Information of China (English)

    杨永杰

    2015-01-01

    Objective Joint analysis glargine Fufangjiakang tablets to treat diabetes with hyperthyroidism clinical results. MethodsRetrospective analysis of December 2012 December -2014 hospital 89 cases of diabetic patients with hyperthyroidism data, divided into two groups according to the different treatment options, the control group of 43 regular routine treatment, research group of 46 routine glargine and Fufangjiakang tablets treatment, blood sugar and complications were observed.ResultsResearch on blood glucose levels were significantly lower than the control group, and the complication rate 6.5% 27.9% lower than the control group, the difference was statistically signiifcant (P<0.05).Conclusion Glargine and compound hyperthyroidism tablet to treat diabetes with hyperthyroidism effect is signiifcant.%目的:分析甘精胰岛素联合复方甲亢片治疗糖尿病伴甲亢的临床效果。方法回顾分析2012年12月~2014年12月本院89例糖尿病伴甲亢患者资料,按不同治疗方案分为两组,对照组43例行常规治疗,研究组46例行甘精胰岛素与复方甲亢片治疗,观察两组血糖及并发症。结果研究组血糖水平均低于对照组,且并发症发生率(6.5%)低于对照组(27.9%),差异具统计学意义(P<0.05)。结论甘精胰岛素与复方甲亢片治疗糖尿病伴甲亢的效果显著。

  7. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  8. Polarised Black Holes in AdS

    CERN Document Server

    Costa, Miguel S; Oliveira, Miguel; Penedones, João; Santos, Jorge E

    2015-01-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global $AdS_{4}$ with conformal boundary $S^{2}\\times\\mathbb{R}_{t}$. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic $AdS$ behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an $AdS$ soliton that includes the full backreaction of the electric field on the $AdS$ geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both $AdS$ soliton and black hole phases. The corresponding phase diagram generalizes the Hawkin...

  9. Constructing Lifshitz solutions from AdS

    CERN Document Server

    Cassani, Davide

    2011-01-01

    Under general assumptions, we show that a gravitational theory in d+1 dimensions admitting an AdS solution can be reduced to a d-dimensional theory containing a Lifshitz solution with dynamical exponent z=2. Working in a d=4, N=2 supergravity setup, we prove that if the AdS background is N=2 supersymmetric, then the Lifshitz geometry preserves 1/4 of the supercharges, and we construct the corresponding Killing spinors. We illustrate these results in examples from supersymmetric consistent truncations of type IIB supergravity, enhancing the class of known 4-dimensional Lifshitz solutions of string theory. As a byproduct, we find a new AdS4 x S1 x T(1,1) solution of type IIB.

  10. Ad Hoc网络%Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    王海涛

    2005-01-01

    首先介绍了Ad Hoc网络的基本概念、技术特点以及关键技术等,然后较为全面地归纳了Ad Hoc网络的典型应用,最后讨论了Ad Hoc网络的发展趋势和有待解决的问题.

  11. Biosimilar Insulin and Costs

    Science.gov (United States)

    Heinemann, Lutz

    2015-01-01

    The costs for insulin treatment are high, and the steady increase in the number of patients with diabetes on insulin presents a true challenge to health care systems. Therefore, all measures to lower these costs are welcomed by patients, physicians, and health care providers. The market introduction of biosimilar insulins presents an option to lower treatment costs as biosimilars are usually offered at a lower price than the originator product. However, the assumption that a drastic reduction in insulin prices will take place, as was observed with many generic drugs, is most probably not realistic. As the first biosimilar insulin has now been approved in the EU, this commentary discusses a number of aspects that are relevant when it comes to the potential cost reduction we will see with the use of biosimilar insulins. PMID:26350722

  12. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... of the patient's reaction to exercise is desirable, which necessitates frequent self-monitoring of plasma glucose. It may often be necessary to diminish the insulin dose before exercise, and/or to ingest additional carbohydrate during or after exercise. In non-insulin-dependent (type II) diabetes, exercise...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so...

  13. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin;

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  14. History of insulin

    Directory of Open Access Journals (Sweden)

    Celeste C. Quianzon

    2012-07-01

    Full Text Available The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP.

  15. Landmarks in Insulin Research

    OpenAIRE

    Ward, Colin W.; Lawrence, Michael C.

    2011-01-01

    Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor.

  16. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action...

  17. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...

  18. Effects of Premix and Basic Insulin on Blood Glucose and Insular B Cell Function of Patients with Type 2 Diabe-tes Mellitus%预混胰岛素和基础胰岛素对2型糖尿病患者血糖及胰岛B细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    戴强; 李红; 钱科威; 李亚娟

    2016-01-01

    Objective To investigate the effects of different types of insulin on blood glucose,gyrated hemoglo-bin(HBA1c)and insular B cell function of patients with primary type 2 diabetes mellitus(T2DM). Methods A total of 90 patients with primary T2DM admitted during June 2013 and Augest 2014 were randomly divided into Novolin 30R group(n = 30),NovoMix 30 group(n = 30)and Glargine group(n = 30). Glargine group was injected with Glargine at the same time every day,and Novolin 30R group was injected with Premixed Insulin( Novolin 30R)at 30 min before breakfast and dinner,and NovoMix 30 group was injected with Insulin Aspart(NovoMix 30 right)right at breakfast and dinner. The body mass index(BMI),levels of HBA1c,triglyceride(TG),total cholesterol(TC)and low-density lipo-protein cholesterol(LDL-C)were tested,and levels of blood glucose and insulin were detected at 0,30,60,120 and 180 min before treatment using oral glucose tolerance test(OGTT)-insulin releasing test,and the insulin resistance index (HOMA-IR)and insular B cell function were evaluated using steady state model for all patients. The above indexes were detected and calculated again after 12 weeks of treatment,and the differences were compared among the 3 groups. Re-sults Compared with those before treatment in the same group,levels of blood glucose,HBA1c and HOMA-IR were sig-nificantly decreased,while the insulin secretion index( HOMA-B)levels were significantly increased in Novolin 30R, NovoMix 30 and Glargine groups after 12 weeks of treatment( P ﹤ 0. 05). BMI and fasting plasma glucose levels in Glargine group were significantly lower than those in the other two groups(P ﹤ 0. 05). The blood glucose level at 60 min before treatment in NovoMix 30 group was significantly lower than those in the other two groups(P ﹤ 0. 01). HOMA-B level in Novolin 30R group was significantly lower than those in the other two groups(P ﹤ 0. 05). The incidence rate of hypoglycemia insulin in Glargine group was significantly

  19. AdS orbifolds and Penrose limits

    Energy Technology Data Exchange (ETDEWEB)

    Alishahiha, Mohsen; Sheikh-Jabbari, Mohammad M.; Tatar, Radu

    2002-12-09

    In this paper we study the Penrose limit of AdS{sub 5} orbifolds. The orbifold can be either in the pure spatial directions or space and time directions. For the AdS{sub 5}/{Lambda} x S{sup 5} spatial orbifold we observe that after the Penrose limit we obtain the same result as the Penrose limit of AdS{sub 5} x S{sup 5}/{Lambda}. We identify the corresponding BMN operators in terms of operators of the gauge theory on R x S{sup 3}/{Lambda}. The semi-classical description of rotating strings in these backgrounds have also been studied. For the spatial AdS orbifold we show that in the quadratic order the obtained action for the fluctuations is the same as that in S{sup 5} orbifold, however, the higher loop correction can distinguish between two cases.

  20. Superradiant instability in AdS

    CERN Document Server

    Ganchev, Bogdan

    2016-01-01

    The phenomenon of superradiance in the context of asymptotically global AdS spacetimes is investigated with particular accent on its effect on the stability of the systems under consideration. To this end, the concept of an asymptotically AdS spacetime is explained, together with its implications on the boundary conditions at $\\mathcal{I}$, as well as the Newman-Penrose-Teukolsky formalism, whereby the Teukolsky master equation in a most general form for Kerr-AdS is given. Furthermore, work done in the cases of RN-AdS and Kerr-AdS is laid out in a concise manner, putting emphasis on the important steps taken in determining the endpoint of the superradiant instability in the two configurations. For the former this turns out to be a black hole with reduced charge and a static charged scalar condensate around it, whereas for the latter two of the more probable outcomes are presented, both of which imply a violation of one of the cosmic censorships.

  1. Preformed Seeds Modulate Native Insulin Aggregation Kinetics.

    Science.gov (United States)

    Dutta, Colina; Yang, Mu; Long, Fei; Shahbazian-Yassar, Reza; Tiwari, Ashutosh

    2015-12-10

    Insulin aggregates under storage conditions via disulfide interchange reaction. It is also known to form aggregates at the site of repeated injections in diabetes patients, leading to injection amyloidosis. This has fueled research in pharmaceutical and biotechnology industry as well as in academia to understand factors that modulate insulin stability and aggregation. The main aim of this study is to understand the factors that modulate aggregation propensity of insulin under conditions close to physiological and measure effect of "seeds" on aggregation kinetics. We explored the aggregation kinetics of insulin at pH 7.2 and 37 °C in the presence of disulfide-reducing agent dithiothreitol (DTT), using spectroscopy (UV-visible, fluorescence, and Fourier transform infrared spectroscopy) and microscopy (scanning electron microscopy, atomic force microscopy) techniques. We prepared insulin "seeds" by incubating disulfide-reduced insulin at pH 7.2 and 37 °C for varying lengths of time (10 min to 12 h). These seeds were added to the native protein and nucleation-dependent aggregation kinetics was measured. Aggregation kinetics was fastest in the presence of 10 min seeds suggesting they were nascent. Interestingly, intermediate seeds (30 min to 4 h incubation) resulted in formation of transient fibrils in 4 h that converted to amorphous aggregates upon longer incubation of 24 h. Overall, the results show that insulin under disulfide reducing conditions at pH and temperature close to physiological favors amorphous aggregate formation and seed "maturity" plays an important role in nucleation dependent aggregation kinetics.

  2. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;

    2013-01-01

    Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage......, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  3. Humanin: a novel central regulator of peripheral insulin action.

    Directory of Open Access Journals (Sweden)

    Radhika H Muzumdar

    Full Text Available BACKGROUND: Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM and Alzheimer's disease (AD. A novel mitochondria-associated peptide, Humanin (HN, has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity. METHODS AND FINDINGS: Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice. CONCLUSIONS: We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM.

  4. Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ai-Qin Song; Li-Rong Sun; Yan-Xia Zhao; Yan-Hua Gao; Lei Chen

    2016-01-01

    Objective: To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A (PPARGC1A) ofrat offspring with gestational diabetes mellitus (GDM). Methods: A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM. A total of 21 pregnant rats with GDM were randomly divided into three groups, with 7 rats in each group, namely the insulin group, metformin group and control group. Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18: 00 every day. Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18: 00 every day, with the first dose of 300 mg/kg. The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L. Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day. After the natural delivery of pregnant rats, 10 offspring rats were randomly selected from each group. At birth, 4 wk and 8 wk after the birth of offspring rats, the weight of offspring rats was measured. The blood glucose level of offspring rats was measured at 4 wk and 8 wk, while the level of serum insulin, triglyceride and leptin was measured at 8 wk.Results: The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group (P0.05). The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group (P0.05). The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P0.05). Insulin and leptin at 8 wk in the insulin group and metformin group were

  5. Boson Stars in AdS

    CERN Document Server

    Buchel, Alex; Lehner, Luis

    2013-01-01

    We construct boson stars in global Anti de Sitter (AdS) space and study their stability. Linear perturbation results suggest that the ground state along with the first three excited state boson stars are stable. We evolve some of these solutions and study their nonlinear stability in light of recent work \\cite{Bizon:2011gg} arguing that a weakly turbulent instability drives scalar perturbations of AdS to black hole formation. However evolutions suggest that boson stars are nonlinearly stable and immune to the instability for sufficiently small perturbation. Furthermore, these studies find other families of initial data which similarly avoid the instability for sufficiently weak parameters. Heuristically, we argue that initial data families with widely distributed mass-energy distort the spacetime sufficiently to oppose the coherent amplification favored by the instability. From the dual CFT perspective our findings suggest that there exist families of rather generic initial conditions in strongly coupled CFT ...

  6. AdS solutions through transgression

    Energy Technology Data Exchange (ETDEWEB)

    Donos, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Gauntlett, J.P. [Imperial College, London (United Kingdom). Blackett Lab.]|[Imperial College, London (United Kingdom). The Institute for Mathematical Sciences; Kim, Nakwoo [Kyung Hee Univ., Seoul (Korea). Dept. of Physics and Research Inst. of Basic Science

    2008-07-15

    We present new classes of explicit supersymmetric AdS{sub 3} solutions of type IIB supergravity with non-vanishing five-form flux and AdS{sub 2} solutions of D=11 supergravity with electric four-form flux. The former are dual to two-dimensional SCFTs with (0,2) supersymmetry and the latter to supersymmetric quantum mechanics with two supercharges. We also investigate more general classes of AdS{sub 3} solutions of type IIB supergravity and AdS{sub 2} solutions of D=11 supergravity which in addition have non-vanishing three-form flux and magnetic four-form flux, respectively. The construction of these more general solutions makes essential use of the Chern-Simons or ''transgression'' terms in the Bianchi identity or the equation of motion of the field strengths in the supergravity theories. We construct infinite new classes of explicit examples and for some of the type IIB solutions determine the central charge of the dual SCFTs. The type IIB solutions with non-vanishing three-form flux that we construct include a two-torus, and after two T-dualities and an S-duality, we obtain new AdS3 solutions with only the NS fields being non-trivial. (orig.)

  7. Insulin initiation and intensification in patients with T2DM for the primary care physician

    Directory of Open Access Journals (Sweden)

    Unger J

    2011-06-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Type 2 diabetes mellitus (T2DM is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C level of 6.5%–7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients' exposure to chronic hyperglycemia and weight gain, and reduce patients' risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena.Keywords: diabetes, basal, bolus, regimens, insulin analogs, structured glucose testing

  8. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  9. Refined Holographic Entanglement Entropy for the AdS Solitons and AdS black Holes

    CERN Document Server

    Ishihara, Masafumi; Ning, Bo

    2012-01-01

    We consider the refinement of the holographic entanglement entropy on a disk region for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss-Bonnet term. The AdS soliton is dual to a gapped system with an IR fixed-point. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy. We then study the renormalization group (RG) flow of the refinement by tuning the linear size of the chosen disk region. Our main results are (i) the RG flow of the refinement decreases monotonically for most of the cases; (ii) there is no topological entanglement entropy for AdS$_5$ soliton even with Gauss-Bonnet correction; (iii) for the AdS black holes, the refinement obeys the volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover; however, the crossover will turn into phase transition by the Gauss-Bonnet correction; (iv) for the AdS solitons, there are discontinuous phase transitions bet...

  10. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  11. An AdS Crunch in Supergravity

    Science.gov (United States)

    Hertog, Thomas

    2004-12-01

    We review some properties of N=8 gauged supergravity in four dimensions with modified, but AdS invariant boundary conditions on the m2 = -2 scalars. There is a one-parameter class of asymptotic conditions on these fields and the metric components, for which the full AdS symmetry group is preserved. The generators of the asymptotic symmetries are finite, but acquire a contribution from the scalar fields. For a large class of such boundary conditions, we find there exist black holes with scalar hair that are specified by a single conserved charge. Since Schwarschild-AdS is a solution too for all boundary conditions, this provides an example of black hole non-uniqueness. We also show there exist solutions where smooth initial data evolve to a big crunch singularity. This opens up the possibility of using the dual conformal field theory to obtain a fully quantum description of the cosmological singularity, and we report on a preliminary study of this.

  12. Low ethanol consumption increases insulin sensitivity in Wistar rats

    Directory of Open Access Journals (Sweden)

    D.T. Furuya

    2003-01-01

    Full Text Available Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05. In addition, an intravenous glucose tolerance test (IVGTT was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05, despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved.

  13. Effect of berberine chloride on expression of insulin degrading enzyme in rat models with AD%小檗碱对阿尔茨海默病大鼠模型胰岛素降解酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱飞奇; 马英; 孙永安; 褚文政; 钱采韵

    2010-01-01

    目的 研究小檗碱对AD大鼠模型胰岛素降解酶(IDE)表达的影响.方法 18只SD大鼠采用完全随机数字表法分为正常组、模型组和小檗碱组,每组6只.正常组不做任何处理,模型组及小檗碱组大鼠通过双侧海马立体定向注射凝聚态Aβ1-40(5 μg)建立AD模型.小檗碱组造模后灌胃给予盐酸小檗碱50mg/kg,1次/d,共14d.采用实时荧光定量PCR法和Western blotting法观察小檗碱对IDE表达的影响.结果 小檗碱组大鼠IDE mRNA的相对拷贝数(45.70±12.80)较正常组(23.40±11.30)及模型组(34.20±6.70)明显增加,小檗碱组大鼠海马IDE蛋白相对表达量(0.61±0.05)较正常组(0.23±0.03)及模型组(0.46±0.07)明显增加,差异均有统计学意义(P<0.05).结论 大鼠海马立体定向注射凝聚态Aβ1-40可以导致海马部位IDE表达增加,小檗碱可以通过促进IDE的表达而促进Aβ的清除.%Objective To explore the effect of berberine chloride on the expression of insulin degrading enzyme (IDE) in the rat models with Alzheimer's disease (AD). Methods Eighteen adult male SD rats, weighting 220-250 g, were randomly divided into normal control group, Aβ1-40 group and Aβ40+berberine chloride group (n=6). The rat models with AD were established by stereotactically injecting condensed Aβ1-40 (5 μg) into the bilateral hippocampus of rats. The rats in the Aβ1-40+berberine chloride group were given berberine chloride (50 mg/kg) by intragastric administration once daily for 14 d. The expressions of IDE were assayed by real time polymerase chain reaction (real-time PCR) and Western blotting. Results The relative quantity of mRNA expression of IDE was (34.2±6.7) in the Aβ1-40+berberine group, which was significantly increased as compared with that in the Aβ1-40 group (45.7±12.8) and normal control group (23.4±11.3, P<0.05). The relative quantity of protein expression of IDE was (0.61 ±0.05) in the Aββ1-40+berberine group, which was significantly

  14. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-11-01

    Full Text Available Abstract Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. Methods A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. Results At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05. However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p2, p Conclusions Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.

  15. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  16. Adding more value to added-value

    DEFF Research Database (Denmark)

    Marian, Livia

    regulation. The results of a qualitative concept test reveal positive attitudes towards the proposed production process. The discussions about fewer standards being sufficient or about options “in-between” conventional and organic standards indicate that the difference in production processes is noticed, yet...... it is probably valued less than expected. The added attributes need to be thoroughly considered when developing and marketing “organic plus” products, as their effect on other product characteristics (e.g. high prices) can detract from their added value....

  17. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    of Biphasic Insulin Aspart 30 treatment has been published recently, these types of guidelines cannot always respond to all of the local requirements. Therefore, it is aimed to prepare a guideline to facilitate the use of Biphasic Insulin Aspart 30 in the right patient, at the right time and in the right manner, as well as to help the physicians. A guideline, aiming to contain current evidences and to meet local requirements, was developed in May and June 2010 by an expert panel composed of experienced endocrinologists working at different parts of Turkey. The guideline includes initial treatment, optimization of initiation dose, and intensification of Biphasic Insulin Aspart 30 during the disease progression. Although previously published global guidelines about initiation, intensification, dose division, dose addition and combination of Biphasic Insulin Aspart 30 with OADs is in applicable situation in general, the content is enlarged by adding some special conditions. Administration information presented in this article forms simply a suggestion rather than a strict recommendation. Since the treatment of every diabetic patient should be individualized, suggestions of this guideline do not have any obligatory power on physicians. Turk Jem 2011; 15: 65-70

  18. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob;

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  19. Probing crunching AdS cosmologies

    Science.gov (United States)

    Kumar, S. Prem; Vaganov, Vladislav

    2016-02-01

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of {N}=8 supergravity on AdS4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã max. Radial geodesics connecting antipodal points necessarily have de Sitter energy Ɛ ≲ ã max, while geodesics with Ɛ > ã max terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved "outward" in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green's function has a branch point determined by ã max which corresponds to the lowest quasinormal frequency.

  20. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  1. Insulin resistance and gray matter volume in neurodegenerative disease.

    Science.gov (United States)

    Morris, J K; Vidoni, E D; Perea, R D; Rada, R; Johnson, D K; Lyons, K; Pahwa, R; Burns, J M; Honea, R A

    2014-06-13

    The goal of this study was to compare insulin resistance in aging and aging-related neurodegenerative diseases, and to determine the relationship between insulin resistance and gray matter volume (GMV) in each cohort using an unbiased, voxel-based approach. Insulin resistance was estimated in apparently healthy elderly control (HC, n=21) and neurodegenerative disease (Alzheimer's disease (AD), n=20; Parkinson's disease (PD), n=22) groups using Homeostasis Model Assessment of Insulin Resistance 2 (HOMA2) and intravenous glucose tolerance test (IVGTT). HOMA2 and GMV were assessed within groups through General Linear Model multiple regression. We found that HOMA2 was increased in both AD and PD compared to the HC group (HC vs. AD, p=0.002, HC vs. PD, p=0.003), although only AD subjects exhibited increased fasting glucose (p=0.005). Furthermore, our voxel-based morphometry analysis revealed that HOMA2 was related to GMV in all cohorts in a region-specific manner (p<0.001, uncorrected). Significant relationships were observed in the medial prefrontal cortex (HC), medial temporal regions (AD), and parietal regions (PD). Finally, the directionality of the relationship between HOMA2 and GMV was disease-specific. Both HC and AD subjects exhibited negative relationships between HOMA2 and brain volume (increased HOMA2 associated with decreased brain volume), while a positive relationship was observed in PD. This cross-sectional study suggests that insulin resistance is increased in neurodegenerative disease, and that individuals with AD appear to have more severe metabolic dysfunction than individuals with PD or PD dementia.

  2. The political attack ad

    Directory of Open Access Journals (Sweden)

    Palma Peña-Jiménez, Ph.D.

    2011-01-01

    Full Text Available During election campaigns the political spot has a clear objective: to win votes. This message is communicated to the electorate through television and Internet, and usually presents a negative approach, which includes a direct critical message against the opponent, rather than an exposition of proposals. This article is focused on the analysis of the campaign attack video ad purposely created to encourage the disapproval of the political opponent among voters. These ads focus on discrediting the opponent, many times, through the transmission of ad hominem messages, instead of disseminating the potential of the political party and the virtues and manifesto of its candidate. The article reviews the development of the attack ad since its first appearance, which in Spain dates back to 1996, when the famous Doberman ad was broadcast, and examines the most memorable campaign attack ads.

  3. Insulin pump therapy in pregnancy.

    Science.gov (United States)

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience.

  4. Probing crunching AdS cosmologies

    CERN Document Server

    Kumar, S Prem

    2015-01-01

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS_4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor a_{max} . Radial geodesics connecting antipodal points necessarily have de Sitter energy E \\leq a_{max}, while geodesics with E > a_{max} terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved "outw...

  5. Twistor methods for AdS$_5$

    CERN Document Server

    Adamo, Tim; Williams, Jack

    2016-01-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS$_5$ is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  6. Holography of AdS vacuum bubbles

    Energy Technology Data Exchange (ETDEWEB)

    Barbon, J.L.F. [Instituto de Fisica Teorica IFT UAM/CSIC, Cantoblanco, Madrid 28049 (Spain); Rabinovici, E. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel)

    2011-07-15

    We consider the fate of AdS vacua connected by tunneling events. A precise holographic dual of thin-walled Coleman-de Luccia bounces is proposed in terms of Fubini instantons in an unstable CFT. This proposal is backed by several qualitative and quantitative checks, including the precise calculation of the instanton action appearing in evaluating the decay rate. Big crunches manifest themselves as time dependent processes which reach the boundary of field space in a finite time. The infinite energy difference involved is identified on the boundary and highlights the ill-defined nature of the bulk setup. We propose a qualitative scenario in which the crunch is resolved by stabilizing the CFT, so that all attempts at crunching always end up shielded from the boundary by the formation of black hole horizons. In all these well defined bulk processes the configurations have the same asymptotics and are finite energy excitations.

  7. Molecular biocoding of insulin

    Directory of Open Access Journals (Sweden)

    Lutvo Kuric

    2010-07-01

    Full Text Available Lutvo KuricNovi Travnik, Kalinska, Bosnia and Herzegovina Abstract: This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid “record”, but also on its structure, configuration, and various shapes. The issue of the existence of an insulin code and coding of the individual structural elements of this protein are discussed. Answers to the following questions are sought. Does the matrix mechanism for biosynthesis of this protein function within the law of the general theory of information systems, and what is the significance of this for understanding the genetic language of insulin? What is the essence of existence and functioning of this language? Is the genetic information characterized only by biochemical principles or it is also characterized by cyberinformation principles? The potential effects of physical and chemical, as well as cybernetic and information principles, on the biochemical basis of insulin are also investigated. This paper discusses new methods for developing genetic technologies, in particular more advanced digital technology based on programming, cybernetics, and informational laws and systems, and how this new technology could be useful in medicine, bioinformatics, genetics, biochemistry, and other natural sciences.Keywords: human insulin, insulin model, biocode, genetic code, amino acids

  8. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Teng Wei-Ping

    2010-11-01

    Full Text Available Abstract Background Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD, the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Results Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Conclusions Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

  9. INSULIN IN THE BRAIN: ITS PATHOPHYSIOLOGICAL IMPLICATIONS FOR STATES RELATED WITH CENTRAL INSULIN RESISTANCE, TYPE 2 DIABETES AND ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    ENRIQUE eBLÁZQUEZ

    2014-10-01

    Full Text Available Although the brain has been considered an insulin-insensitive organ, recent reports on the location of insulin and its receptors in the brain have introduced new ways of considering this hormone responsible for several functions. The origin of insulin in the brain has been explained from peripheral or central sources, or both. Regardless of whether insulin is of peripheral origin or produced in the brain, this hormone may act through its own receptors present in the brain. The molecular events through which insulin functions in the brain are the same as those operating in the periphery. However, certain insulin actions are different in the CNS, such as hormone-induced glucose uptake due to a low insulin-sensitive GLUT-4 activity, and because of the predominant presence of GLUT-1 and GLUT-3. In addition, insulin in the brain contributes to the control of nutrient homeostasis, reproduction, cognition and memory, as well as to neurotrophic, neuromodulatory, and neuroprotective effects. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes (T2DM and Alzheimer’s disease (AD. A close association between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients, and some authors have proposed the name type 3 diabetes for this association. There are links between AD and type 2 diabetes mellitus (T2DM through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein OGlcNAcylation, formation of amyloid plaques, altered Aβ metabolism, and tau hyperphosphorylation. Advances in the knowledge of preclinical AD and T2DM may be a major stimulus for the development of treatment for preventing the pathogenic events of

  10. Skil problemerne ad

    DEFF Research Database (Denmark)

    Kaspersen, Peter

    2007-01-01

    På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger.......På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger....

  11. 胰岛素类似物联合口服降糖药治疗2型糖尿病%Insulin analogs combined with oral antidiabetic drugs in treating patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    周泽华; 肖蓉; 何煦; 瞿文娟; 杨刚毅; 李伶; 李志勇

    2013-01-01

    目的:评估3种胰岛素类似物(地特胰岛素、甘精胰岛素、双相门冬胰岛素30)联合口服降糖药用于治疗血糖控制欠佳的2型糖尿病患者的有效性及安全性.方法:73例血糖控制不达标的2型糖尿病患者被分为3组:每日睡前1次地特胰岛素组(n=23),每日睡前1次甘精胰岛素组(n=27)和每日早晚餐前各1次双相门冬胰岛素30组(n=23),各组均联合使用口服降糖药,共治疗16周.分析比较3组患者治疗前后糖化血红蛋白(hemoglobin A1c,HbA1c)、空腹血糖(fasting blood glucose,FBG)、餐后血糖(postprandial blood glucose,PBG)、体质指数(body mass index,BMI)的变化.评估3组间HbA1c、FBG、PBG下降幅度、HbA1c达标率(<7%)和低血糖事件的发生率.结果:治疗前3组HbA1c、FBG、PBG均无显著差异.经16周治疗,3组HbA1c、FBG、PBG均较治疗前显著下降(P<0.01),但组间比较无显著差异(P>0.05).各组治疗前后BMI均无显著变化(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组HbA1c达标率(<7%)分别为43%、59%、52%,组间比较无显著差异(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组分别发生3例(13%)、2例(7%)、5例(22%)轻度低血糖,均无严重低血糖事件发生,各组间低血糖发生率无显著差异(P>0.05).结论:在本研究人群中,有效控制FBG是HbA1c降低及达标的有效手段,3种胰岛素类似物联合口服降糖治疗2型糖尿病,可达到同样的降糖效果,并且体质量无明显增加、低血糖发生率较低.%Objective:To evaluate the efficacy and safety of insulin analogs (Insulin detemir,Insulin glargine,B iphasic insulin aspart 30) combined with oral antidiabetic drugs(OADs) in treating type 2 diabetic mellitus patients whose blood glucose is insufficiently controlled.Methods:Seventy-three type 2 diabetic mellitus patients with insufficiently controlled blood glucose were assigned to three groups

  12. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B;

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  13. Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

    Directory of Open Access Journals (Sweden)

    Gregory E Peterson

    2009-05-01

    Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

  14. Insulin C-peptide test

    Science.gov (United States)

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

  15. Mobile ad hoc networking

    CERN Document Server

    John Wiley & Sons

    2004-01-01

    "Assimilating the most up-to-date information on research and development activities in this rapidly growing area, Mobile Ad Hoc Networking covers physical, data link, network, and transport layers, as well as application, security, simulation, and power management issues in sensor, local area, personal, and mobile ad hoc networks. Each of the book's sixteen chapters has been written by a top expert and discusses in-depth the most important topics in the field. Mobile Ad Hoc Networking is an excellent reference and guide for professionals seeking an in-depth examination of topics that also provides a comprehensive overview of the current state-of-the-art."--Jacket.

  16. [Treatment by external insulin pump].

    Science.gov (United States)

    Clavel, Sylvaine

    2010-12-01

    Since the recent recommendations by the French speaking association for research on diabetes and metabolic illnesses (Alfediam), treatment by insulin pump has found itself in competition with basal-bolus, a procedure using similar injections of insulin which has become a benchmark treatment. The latest Alfediam guidelines focus on defining ways of treating diabetics with an external insulin pump.

  17. Early insulin therapy Coordination Council

    Directory of Open Access Journals (Sweden)

    Marina Vladimirovna Shestakova

    2012-12-01

    Full Text Available Coordination Council has denoted the importance of adherence to Russian and international guidelines and prominent role of insulin therapy in management of type 2 diabetes mellitus (T2DM. Insulin therapy in T2DM preserves endogenous insulin secretion, prevents or decelerates development of microvascular complications and is known to be the most effective glucose-lowering treatment.

  18. Value Adding Management

    DEFF Research Database (Denmark)

    Jensen, Per Anker; Katchamart, Akarapong

    2011-01-01

    Purpose: To investigate how Facilities Management (FM) can add value and develop a management concept that can assist facilities managers in implementing value adding strategies and practices. Theory: The study is based on the management model for FM included in the European FM standards, recent...... theories on added value of FM and real estate and the related concept of Value Management from building projects. The study is related to the EuroFM research group on The Added Value of FM. Design/methodology/approach: The study outlines a preliminary theoretical based management concept, which...... is investigated, tested and discussed based on a case study of an international corporation. Findings: The study shows that the management model for FM creates a relevant starting point but also that stakeholder and relationship management is an essential aspect of Value Adding Management. The case study confirms...

  19. Antiproton-Decelerator (AD)

    CERN Multimedia

    Laurent Guiraud

    1998-01-01

    When the Low-Energy Antiproton Ring (LEAR) was stopped in 1996, because of its costly operation, a cheaper way of continuing low-energy antiproton physics was sought. The Antiproton-Collector (AC), added in 1987 to the Antiproton Accumulator (AA) to provide a tenfold intensity increase, was converted into the Antiproton-Decelerator (AD). Antiprotons from the target at 3.5 GeV/c are decelerated to 100 MeV/c, and fast-ejected to the experiments. Major changes were necessary. Above all, the conversion from a constant-field machine to one with a magnetic cycle, modulating the field by an impressive factor 35. New systems for stochastic and electron cooling had to be added. Beam diagnostics at an intensity of only 2E7 antiprotons was a challenge. In 2000, the AD began delivery of antiprotons to the experiments.

  20. AdS_3: the NHEK generation

    CERN Document Server

    Bena, Iosif; Puhm, Andrea

    2015-01-01

    It was argued in arXiv:1203.4227 that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically-AdS_3 x S^3/Z_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  1. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... symptoms. Scientists have found that complex interactions in fat tissue draw immune cells to the area and trigger low-level chronic inflammation. This inflammation can contribute to the development of insulin resistance, type 2 diabetes, and CVD. Studies show that losing ...

  2. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

  3. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  4. Insulin Signalling: The Inside Story.

    Science.gov (United States)

    Posner, Barry I

    2017-02-01

    Insulin signalling begins with binding to its cell surface insulin receptor (IR), which is a tyrosine kinase. The insulin receptor kinase (IRK) is subsequently autophosphorylated and activated to tyrosine phosphorylate key cellular substrates that are essential for entraining the insulin response. Although IRK activation begins at the cell surface, it is maintained and augmented following internalization into the endosomal system (ENS). The peroxovanadium compounds (pVs) were discovered to activate the IRK in the absence of insulin and lead to a full insulin response. Thus, IRK activation is both necessary and sufficient for insulin signalling. Furthermore, this could be shown to occur with activation of only the endosomal IRK. The mechanism of pV action was shown to be the inhibition of IRK-associated phosphotyrosine phosphatases (PTPs). Our studies showed that the duration and intensity of insulin signalling are modulated within ENS by the recruitment of cellular substrates to ENS; intra-endosomal acidification, which promotes dissociation of insulin from the IRK; an endosomal acidic insulinase, which degrades intra-endosomal insulin; and IRK-associated PTPs, which dephosphorylate and, hence, deactivate the IRK. Therefore, the internalization of IRKs is central to insulin signalling and its regulation.

  5. Heat shock response and insulin-associated neurodegeneration.

    Science.gov (United States)

    Urban, Michael J; Dobrowsky, Rick T; Blagg, Brian S J

    2012-03-01

    Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN), Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). Despite their prevalence, there are limited therapeutic options available for the treatment of these neurodegenerative disorders. Therefore, establishing a link between insulin/IGF-I and the pathoetiology of these diseases may provide alternative approaches toward their management. Many of the heat shock proteins (Hsps) are well-known molecular chaperones that solubilize and clear damaged proteins and protein aggregates. Recent studies suggest that modulating Hsps may represent a promising therapeutic avenue for improving insulin and IGF-I signaling. Pharmacological induction of the heat shock response (HSR) may intersect with insulin/IGF-I signaling to improve aspects of neurodegenerative phenotypes. Herein, we review the intersection between Hsps and the insulin/IGF systems under normal and pathological conditions. The discussion will emphasize the potential of non-toxic HSR inducers as viable therapeutic agents.

  6. Eating ad Libitum

    DEFF Research Database (Denmark)

    Hillersdal, Line

    in the context of the 'ad libitum meal'. The analytical interest is thus what kind of eaters and bodies are enacted in the meal test and what ideas of prevention and treatment are embedded in their standards. Drawing from ongoing empirical work among Danish obesity researchers performing scientific meal tests I...... ask what make up food stuff and eaters in the meal tests? More specifically I explore a scientific testing of changes in taste preferences before and after weight-loss surgery using an ad libitum buffet with a selection of different foods and another testing the effect of exercise on appetite also...... using an ad libitum meal consisting of spaghetti bolognaise. I analyse the entanglement and concurrence of different knowledge practices and show how several scalings of appetite play out, one ex explaining the aim of the test, being to ”measure what your body would want the most” and hence producing...

  7. Dynamic ad hoc networks

    CERN Document Server

    Rashvand, Habib

    2013-01-01

    Motivated by the exciting new application paradigm of using amalgamated technologies of the Internet and wireless, the next generation communication networks (also called 'ubiquitous', 'complex' and 'unstructured' networking) are changing the way we develop and apply our future systems and services at home and on local, national and global scales. Whatever the interconnection - a WiMAX enabled networked mobile vehicle, MEMS or nanotechnology enabled distributed sensor systems, Vehicular Ad hoc Networking (VANET) or Mobile Ad hoc Networking (MANET) - all can be classified under new networking s

  8. Initiation of insulin glargine in patients with Type 2 diabetes in suboptimal glycaemic control positively impacts health-related quality of life. A prospective cohort study in primary care

    DEFF Research Database (Denmark)

    Hajós, Tibor R S; Pouwer, F; de Grooth, R;

    2011-01-01

    completed self-report health-related quality of life measures, including emotional well-being (World Health Organization-5 well-being index), fear of hypoglycaemia (Hypoglycaemia Fear Survey) and diabetes symptom distress (Diabetes Symptom Checklist-revised). Data were analysed using generalized estimating.......004); no significant changes in self-reported symptomatic and severe hypoglycaemia were observed, while nocturnal hypoglycaemia slightly decreased. The Hypoglycaemia Fear Survey score decreased from 14.6 ± 16.2 to 12.1 ± 15.2 and 10.8 ± 14.4 at 3 and 6 months, respectively (P

  9. Insulin/receptor binding: the last piece of the puzzle? What recent progress on the structure of the insulin/receptor complex tells us (or not) about negative cooperativity and activation.

    Science.gov (United States)

    De Meyts, Pierre

    2015-04-01

    Progress in solving the structure of insulin bound to its receptor has been slow and stepwise, but a milestone has now been reached with a refined structure of a complex of insulin with a "microreceptor" that contains the primary binding site. The insulin receptor is a dimeric allosteric enzyme that belongs to the family of receptor tyrosine kinases. The insulin binding process is complex and exhibits negative cooperativity. Biochemical evidence suggested that insulin, through two distinct binding sites, crosslinks two receptor sites located on each α subunit. The structure of the unliganded receptor ectodomain showed a symmetrical folded-over conformation with an antiparallel disposition. Further work resolved the detailed structure of receptor site 1, both without and with insulin. Recently, a missing piece in the puzzle was added: the C-terminal portion of insulin's B-chain known to be critical for binding and negative cooperativity. Here I discuss these findings and their implications.

  10. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  11. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  12. Localization on $AdS_2\\times S^1$

    CERN Document Server

    David, Justin R; Gupta, Rajesh Kumar; Narain, Kumar

    2016-01-01

    Conformal symmetry relates the metric on $AdS_2 \\times S^{1}$ to that of $S^3$. This implies that under a suitable choice of boundary conditions for fields on $AdS_2$ the partition function of conformal field theories on these spaces must agree which makes $AdS_2 \\times S^{1}$ a good testing ground to study localization on non-compact spaces. We study supersymmetry on $AdS_2\\times S^1$ and determine the localizing Lagrangian for ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2\\times S^1$. We evaluate the partition function of ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2 \\times S^1$ using localization, where the radius of $S^1$ is $q$ times that of $AdS_2$. With boundary conditions on $AdS_2\\times S^1$ which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in $AdS_2$, the result for the partition function precisely agrees with that of the theory on the $q$-fold covering of $S^3$.

  13. D-branes in Lorentzian AdS(3)

    CERN Document Server

    Israel, D

    2005-01-01

    We study the exact construction of D-branes in Lorentzian AdS(3). We start by defining a family of conformal field theories that gives a natural Euclidean version of the SL(2,R) CFT and does not correspond to H(3)+, the analytic continuation of AdS(3). We argue that one can recuperate the exact CFT results of Lorentzian AdS(3), upon an analytic continuation in the moduli space of these conformal field theories. Then we construct exact boundary states for various symmetric and symmetry-breaking D-branes in AdS(3).

  14. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin

    Directory of Open Access Journals (Sweden)

    Schweizer A

    2013-02-01

    Full Text Available Anja Schweizer,1 James E Foley,2 Wolfgang Kothny,2 Bo Ahrén31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Department of Clinical Sciences, Lund University, Lund, SwedenAbstract: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4 inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with

  15. Combining a GLP-1 receptor agonist and basal insulin: study evidence and practical considerations.

    Science.gov (United States)

    Carris, Nicholas W; Taylor, James R; Gums, John G

    2014-12-01

    Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.

  16. The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour

    NARCIS (Netherlands)

    de Boer, Stefanie Amarens; Lefrandt, Joop Daniel; Petersen, Japke Frida; Boersma, Hendrikus Hessel; Mulder, Douwe Johannes; Hoogenberg, Klaas

    2016-01-01

    Background Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes patients have shown to lower body weight, improve glycaemic control and reduce total daily insulin dose in short term studies, although the individual response greatly varies. Objective To evaluate GL

  17. Insulin Neuroprotection and the Mechanisms

    Institute of Scientific and Technical Information of China (English)

    Li-Yun Yu; Yu Pei

    2015-01-01

    Objective:To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.Data Sources:The study is based on the data from PubMed.Study Selection:Articles were selected with the search terms "insulin","blood glucose","neuroprotection","brain","glycogen","cerebral ischemia","neuronal necrosis","glutamate","γ-aminobutyric acid".Results:Insulin has neuroprotection.The mechanisms include the regulation of neurotransmitter,promoting glycogen synthesis,and inhibition of neuronal necrosis and apoptosis.Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.Conclusions:Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.

  18. Ads in Indonesia

    Directory of Open Access Journals (Sweden)

    Wulan Roro Retno

    2017-01-01

    Full Text Available Cosmetics industry created the beauty myth for women through advertising. A cosmetic ad in Indonesia has spread a new concept of white skin: East Asia beauty myth. The white concept of Asia white skin basically derived from colonial legacy. The purpose of the research was analyzing the beauty myth in Indonesia ads using postcolonial perspective. The principal result brought the discourse analysis and postcolonial perspective a new insight in communication research. Particularly on media and cultural studies. Major conclusions showed that the beauty myth since the Dutch colonial period never been change. The main concept is always in colonialism’s idea: “white is better”. The West is better than the East.

  19. Adding linear orders

    CERN Document Server

    Shelah, Saharon

    2011-01-01

    We address the following question: Can we expand an NIP theory by adding a linear order such that the expansion is still NIP? Easily, if acl(A)=A for all A, then this is true. Otherwise, we give counterexamples. More precisely, there is a totally categorical theory for which every expansion by a linear order has IP. There is also an \\omega-stable NDOP theory for which every expansion by a linear order interprets bounded arithmetic.

  20. Diabetic lipohypertrophy delays insulin absorption.

    Science.gov (United States)

    Young, R J; Hannan, W J; Frier, B M; Steel, J M; Duncan, L J

    1984-01-01

    The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 +/- 3.5 +/- SEM) control; 35.3 +/- 3.9 lipohypertrophy, P less than 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.

  1. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...

  2. TLR4 and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Jane J. Kim

    2010-01-01

    Full Text Available Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4, involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide and endogenous ligands (e.g., free fatty acids which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.

  3. AdS 3-manifolds and Higgs bundles

    DEFF Research Database (Denmark)

    Alessandrini, Daniele; Li, Qiongling

    2015-01-01

    In this paper we investigate the relationships between closed AdS 3-manifolds and Higgs bundles. We have a new way to construct AdS structures that allows us to see many of their properties explicitly, for example we can recover the very recent formula by Tholozan for the volumes. We also find...

  4. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    Science.gov (United States)

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.

  5. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome

    OpenAIRE

    Kim, Bhumsoo; Feldman, Eva L.

    2015-01-01

    Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and ...

  6. Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Jaeseok Han; Eung-Hwi Kim; Woohyuk Choi; Hee-Sook Jun

    2012-01-01

    AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Leprdb/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk (AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC:9150.17±1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

  7. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...

  8. Intensive Insulin Therapy: Tight Blood Sugar Control

    Science.gov (United States)

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  9. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T;

    2015-01-01

    diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad...

  10. Pathologies in Lovelock AdS Black Branes and AdS/CFT

    CERN Document Server

    Takahashi, Tomohiro

    2011-01-01

    We study the pathologies in AdS black branes in Lovelock theory. More precisely, we examine the conditions that AdS black branes have the naked singularity, the ghost instability and the dynamical instability. From the point of view of the AdS/CFT correspondence, the pathologies in AdS black branes indicate the pathologies in the corresponding CFT. Hence, we need to be careful when we apply AdS/CFT in Lovelock theory to various phenomena such as the shear viscosity to entropy ratio in strongly coupled quantum filed theory.

  11. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  12. The effect of Ad

    Institute of Scientific and Technical Information of China (English)

    李小艳

    2010-01-01

    There is the trend that now people appreciate those who are slim and regard slim even thin people beautiful. The thinner a person is, the more beautiful. Women, born to pursuit beauty, try various means to follow the trend. We all watch TV, and find a lot of advertisements on diet. The effect of them is tremendous. We all know the fact that it is not at all the better mouse trap will catch mouse. The sales methods are more important. If an advertisement is very interesting and seemingly effective, people will be lured by the ad and then try some of the products.

  13. Management job ads

    DEFF Research Database (Denmark)

    2014-01-01

    The article asks whether it is not the responsibility of corporations to address the issue of women being underrepresented in Danish management jobs. In other words, it is argued that corporations should be encouraged to engage more actively in the recruitment of both men and women for management...... that this agreement reflects a high degree of conservatism in the system where men enjoy a considerable advantage and where procedures that ensure male dominance are perpetuated even in the linguistic and discursive construction of job ads....

  14. Role of insulin and insulin receptor in learning and memory.

    Science.gov (United States)

    Zhao, W Q; Alkon, D L

    2001-05-25

    As one of the most extensively studied protein hormones, insulin and its receptor have been known to play key roles in a variety of important biological functions. Until recent years, the functions of insulin and insulin receptor (IR) in the central nervous system (CNS) have largely remained unclear. IR is abundantly expressed in several specific brain regions that govern fundamental behaviors such as food intake, reproduction and high cognition. The IR from the periphery and CNS exhibit differences in both structure and function. In addition to that from the peripheral system, locally synthesized insulin in the brain has also been identified. Accumulated evidence has demonstrated that insulin/IR plays important roles in associative learning, as suggested by results from both interventive and correlative studies. Interruption of insulin production and IR activity causes deficits in learning and memory formation. Abnormal insulin/IR levels and activities are seen in Alzheimer's dementia, whereas administration of insulin significantly improves the cognitive performance of these patients. The synaptic bases for the action of insulin/IR include modifying neurotransmitter release processes at various types of presynaptic terminals and modulating the activities of both excitatory and inhibitory postsynaptic receptors such as NMDA and GABA receptors, respectively. At the molecular level, insulin/IR participates in regulation of learning and memory via activation of specific signaling pathways, one of which is shown to be associated with the formation of long-term memory and is composed of intracellular molecules including the shc, Grb-r/SOS, Ras/Raf, and MEK/MAP kinases. Cross-talk with another IR pathway involving IRS1, PI3 kinase, and protein kinase C, as well as with the non-receptor tyrosine kinase pp60c-src, may also be associated with memory processing.

  15. Lacrimal gland primary acinar cell culture: the role of insulin

    Directory of Open Access Journals (Sweden)

    Leonardo Tannus Malki

    2016-04-01

    Full Text Available ABSTRACT Purpose: The goal of the present study was to establish a protocol for primary culture of lacrimal gland acinar cells (LGACs and to assess the effect of adding insulin to the culture media. Methods: LGACs were isolated and cultured from lacrimal glands of Wistar male rats. The study outcomes included cell number, viability, and peroxidase release over time and in response to three concentrations of insulin (0.5, 5.0, and 50.0 μg/mL. Results: In LGAC primary culture, cells started to form clusters by day 3. There was a time-response pattern of peroxidase release, which rose by day 6, in response to carbachol. Culture viability lasted for 12 days. An insulin concentration of 5.0 μg/mL in the culture medium resulted in higher viability and secretory capacity. Conclusions: The present method simplifies the isolation and culture of LGACs. The data confirmed the relevance of adding insulin to maintain LGACs in culture.

  16. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M

    2008-01-01

    OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...... glucose tolerance test (P insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0...

  17. Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

    Science.gov (United States)

    Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

    2017-05-01

    In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

  18. Insulin Signaling and Heart Failure.

    Science.gov (United States)

    Riehle, Christian; Abel, E Dale

    2016-04-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin-resistant states such as type 2 diabetes mellitus and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes mellitus alters the systemic and neurohumoral milieu, leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead box O transcriptional signaling or glucose transport, which may also impair cardiac metabolism, structure, and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed.

  19. [Local lipohypertrophy in insulin treatment].

    Science.gov (United States)

    Herold, D A; Albrecht, G

    1993-01-01

    Local lipoatrophy and lipohypertrophy at injection sites are well known side effects of treatment with insulin. Conditions favouring these local complications are created when repeated or continuous injections are given into the same areas. We report on a 27-year-old female patient who suffered from persistent local swellings after use of an external pump which continuously injected human insulin via indwelling cannulas.

  20. Value-Added Exchange Rates

    OpenAIRE

    Rudolfs Bems; Robert C. Johnson

    2012-01-01

    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  1. High Dose Astaxanthin Lowers Blood Pressure and Increases Insulin Sensitivity in Rats: Are These Effects Interdependent?

    Directory of Open Access Journals (Sweden)

    Harry G. Preuss, Bobby Echard, Eiji Yamashita, Nicholas V. Perricone

    2011-01-01

    Full Text Available The present investigation in Sprague-Dawley rats (SD was designed to examine effects of astaxanthin (Asta at different doses on elevated blood pressure (BP and glucose-insulin perturbations produced by heavy sucrose ingestion. We also examined effects of Asta on BP during restraint stress. SD were divided into six groups each containing eight rats. All SD ate a basic diet of ground regular rat chow with sucrose added at 30% w/w. The Control group received only the basic diet containing added sucrose, while the other five groups each received the same diet with added test material: captopril, (30 mg/Kg, pioglitazone (15.0 mg/Kg, low Asta (25 mg/Kg, medium Asta (50 mg/kg or high Asta (100 mg/Kg. Many tests were carried out to examine the mechanisms behind the effects of Asta on BP (serum ACE activity, losartan challenge, and LNAME challenge and the glucose-insulin system (glucose tolerance, HOMA measurement, and insulin challenge. In SD, a relatively low dose of Asta decreased SBP, but produced no major changes in the glucose-insulin system simulating results from a previous study using Zucker Fatty Rats. Increasing the dose of Asta resulted in both a lowering of elevated systolic BP and enhanced insulin sensitivity determined by many different estimations. BP lowering was consistent with changes in the renin-angiotensin (RAS and nitric oxide (NO systems. At the examined doses of each, captopril lowered BP in SD without influencing glucose-insulin metabolism, whereas pioglitazone favorably affected glucose-insulin metabolism while showing essentially no effects on BP. Accordingly, Asta beneficially affects both sucrose-induced elevations of BP and insulin resistance at relatively high doses in SD. Also, Asta at higher doses lessens restraint stress, whereas, captopril and pioglitazone did not at the doses examined, even though they influenced the BP and glucose-insulin systems respectively.

  2. Abnormal insulin levels and vertigo.

    Science.gov (United States)

    Proctor, C A

    1981-10-01

    Fifty patients with unexplained vertigo (36) or lightheadedness (14) are evaluated, all of whom had abnormal ENGs and normal audiograms. Five hour insulin glucose tolerance tests were performance on all patients, with insulin levels being obtained fasting and at one-half, one, two, and three hours. The results of this investigation were remarkable. Borderline or abnormal insulin levels were discovered in 82% of patients; 90% were found to have either an abnormal glucose tolerance test or at least borderline insulin levels. The response to treatment in these dizzy patients was also startling, with appropriate low carbohydrate diets improving the patient's symptoms in 90% of cases. It is, therefore, apparent that the earliest identification of carbohydrate imbalance with an insulin glucose tolerance test is extremely important in the work-up of the dizzy patients.

  3. The SWITCH study (sensing with insulin pump therapy to control HbA(1c))

    DEFF Research Database (Denmark)

    Conget, Ignacio; Battelino, Tadej; Giménez, Marga

    2011-01-01

    studies investigating the effect of real-time continuous glucose monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1 diabetes are increasing. Pump therapy is well established as a "gold standard" for insulin delivery, offering improvements over multiple daily insulin inject......]) study is a multicenter, randomized, controlled, crossover study to evaluate if adding CGM to experienced pump patients with suboptimal metabolic control will provide additional insight enabling clinical and therapeutic benefit....

  4. Natural origin immunomodulators influence on insulin content in broiler chickens blood under stress

    OpenAIRE

    Степан Стефанович Грабовський

    2014-01-01

    The results of determination of protein fractions content insulin and protein concentrations in plasma of broiler chickens, which further added to the feed of natural origin biologically active substances is given. As an antistressors and immunomodulators in pre-slaughter period biologically active substances of spleen extract were obtained with and without ultrasound application. Aerosol introduction of spleen extract to the broiler chickens feed increases the insulin concentration in broile...

  5. An $xp$ model on $AdS_2$ spacetime

    CERN Document Server

    Molina-Vilaplana, Javier

    2013-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, equal in magnitude, given by a harmonic oscillator with a zero point energy parameterized by the AdS radius, measured in units of a fundamental length of the model. We also construct the generators of the isometry group SO(2,1) of the AdS$_2$ spacetime, and discuss the relation with conformal quantum mechanics.

  6. Needle-free insulin drug delivery

    Directory of Open Access Journals (Sweden)

    Patni Preeti

    2006-01-01

    Full Text Available For most patients with type 1 diabetes, the worst part of the disease is to tolerate needle after needle, both for glucose measurement and to deliver insulin. In the last two decades, concept of insulin therapy by multiple-dose injection has undergone a miraculous change. Needle-free insulin delivery appeared to be a wonderful approach, and its allure rested in being comfortable and safe. In today′s era, insulin delivery by alternative route is a topic of current interest in the design of drug delivery system. Major global pharmaceutical companies are showing encouraging progress in their attempts to develop alternative insulin delivery technologies. Many such drug delivery systems have been developed for oral, buccal and nasal route. This review article discusses, in brief, the novel and emerging technologies that are in pipeline, including insulin inhalers, insulin spray, insulin pill, insulin analogues, insulin complement, islet cell transplant, implantable insulin pumps and guardian continuous glucose monitoring system.

  7. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  8. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

    DEFF Research Database (Denmark)

    de Rooij, Susanne R; Dekker, Jacqueline M; Kozakova, Michaela;

    2009-01-01

    OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...

  9. Dressing phases of AdS3/CFT2

    CERN Document Server

    Borsato, Riccardo; Sfondrini, Alessandro; Stefanski, Bogdan; Torrielli, Alessandro

    2013-01-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3 x S3 x T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly-coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their sub-leading order and compare it with recent one-loop perturbative results, and co

  10. Dressing phases of AdS3/CFT2

    Science.gov (United States)

    Borsato, Riccardo; Ohlsson Sax, Olof; Sfondrini, Alessandro; Stefański, Bogdan, Jr.; Torrielli, Alessandro

    2013-09-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3×S3×T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their subleading order and compare it with recent one-loop perturbative results and comment on their weak-coupling expansion.

  11. Insulin sensitivity is normalized in the third generation (F3 offspring of developmentally programmed insulin resistant (F2 rats fed an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Martin John F

    2008-10-01

    Full Text Available Abstract Background/Aims The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Methods Female Sprague Dawley rats (F0 were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. Results F2 animals fed energy-restricted diets were insulin resistant (p ad libitum postweaning diets (p Conclusion Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.

  12. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  13. Chaos and hydrodynamics near AdS$_2$

    CERN Document Server

    Jensen, Kristan

    2016-01-01

    We revisit AdS$_2$ holography with the Sachdev-Ye-Kitaev models in mind. Our main result is to rewrite a generic theory of gravity near an AdS$_2$ throat as a novel hydrodynamics coupled to the correlation functions of a conformal quantum mechanics. This gives a prescription for the computation of $n$-point functions in the dual quantum mechanics. We thereby find that the dual is maximally chaotic.

  14. Quantum Field Theory and Unification in AdS5

    CERN Document Server

    Randall, Lisa; Randall, Lisa; Schwartz, Matthew D.

    2001-01-01

    We consider gauge bosons in the bulk of AdS5 in a two-brane theory that addresses the hierarchy problem. We show such a theory can be consistent with gauge coupling unification at a high scale. We discuss subtleties in this calculation and show how to regulate consistently in a bounded AdS5 background. Our regularization is guided by the holographic dual of the calculation.

  15. Supersymmetry of AdS and flat IIB backgrounds

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2015-02-01

    We present a systematic description of all warped AdS n × w M 10- n and IIB backgrounds and identify the a priori number of supersymmetries N preserved by these solutions. In particular, we find that the AdS n backgrounds preserve for n ≤ 4 and for 4 < n ≤ 6 supersymmetries and for suitably restricted. In addition under some assumptions required for the applicability of the maximum principle, we demonstrate that the Killing spinors of AdS n backgrounds can be identified with the zero modes of Dirac-like operators on M 10- n establishing a new class of Lichnerowicz type theorems. Furthermore, we adapt some of these results to backgrounds with fluxes by taking the AdS radius to infinity. We find that these backgrounds preserve for 2 < n ≤ 4 and for 4 < n ≤ 7 supersymmetries. We also demonstrate that the Killing spinors of AdS n × w M 10- n do not factorize into Killing spinors on AdS n and Killing spinors on M 10- n .

  16. Metabolic regulation of insulin secretion.

    Science.gov (United States)

    Keane, Kevin; Newsholme, Philip

    2014-01-01

    Regulation of metabolic fuel homeostasis is a critical function of β-cells, which are located in the islets of Langerhans of the animal pancreas. Impairment of this β-cell function is a hallmark of pancreatic β-cell failure and may lead to development of type 2 diabetes mellitus. β-Cells are essentially "fuel sensors" that monitor and react to elevated nutrient load by releasing insulin. This response involves metabolic activation and generation of metabolic coupling factors (MCFs) that relay the nutrient signal throughout the cell and induce insulin biosynthesis and secretion. Glucose is the most important insulin secretagogue as it is the primary fuel source in food. Glucose metabolism is central to generation of MCFs that lead to insulin release, most notably ATP. In addition, other classes of nutrients are able to augment insulin secretion and these include members of the lipid and amino acid family of nutrients. Therefore, it is important to investigate the interplay between glucose, lipid, and amino acid metabolism, as it is this mixed nutrient sensing that generate the MCFs required for insulin exocytosis. The mechanisms by which these nutrients are metabolized to generate MCFs, and how they impact on β-cell insulin release and function, are discussed in detail in this article.

  17. Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells.

    Science.gov (United States)

    Najem, Dema; Bamji-Mirza, Michelle; Yang, Ze; Zhang, Wandong

    2016-06-01

    Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) toxicity, tau pathology, insulin resistance, neuroinflammation, and dysregulation of cholesterol homeostasis, all of which play roles in neurodegeneration. Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes. In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ42 on these pathways in vitro. We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid-β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a cells. Treatment of human neuroblastoma SH-SY5Y cells with Aβ42 also increased p-IRS-S612, suggesting that Aβ42 is responsible for insulin resistance. The insulin resistance was alleviated when N2a-AβPP cells were treated with higher insulin concentrations. Insulin increased Aβ release from N2a-AβPP cells, by which it may promote Aβ clearance. Insulin increased cholesterol-synthesis gene expression in SH-SY5Y and N2a cells, including 24-dehydrocholesterol reductase (DHCR24) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) through sterol-regulatory element-binding protein-2 (SREBP2). While Aβ42-treated SH-SY5Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses, they also showed down-regulation of neuro-protective/anti-inflammatory DHCR24. These results suggest that Aβ42 may cause insulin resistance, activate JNK for c-Jun phosphorylation, and lead to dysregulation of cholesterol homeostasis, and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote A

  18. Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions.

    Science.gov (United States)

    Cartmill, J A; Thompson, D L; Storer, W A; Crowley, J C; Huff, N K; Waller, C A

    2005-08-01

    Three experiments tested the hypotheses that daily cortisol rhythm, feeding time, and/or insulin infusion affect(s) leptin secretion in stallions. Ten mature stallions received ad libitum hay and water and were fed a grain concentrate once daily at 0700. In Exp. 1, stallions received either a single injection of dexamethasone (125 microg/kg BW i.m.; n = 5) or vehicle (controls; n = 5) at 0700 on d -1. Starting 24 h later, blood samples were collected every 2 h for 36 h via jugular venipuncture. Cortisol in control stallions varied (P infusion of insulin (1.2 mIU.kg BW(-1).min(-1)) for 180 min, which was gradually decreased to 0 by 240 min; sufficient glucose was infused to maintain euglycemia. Plasma insulin increased (P infused with insulin and glucose (to approximately 75 microIU/mL), but insulin remained low (10 microIU/mL or less) when they were not fed. The increases in insulin were paralleled by gradual increases (P infused with insulin and glucose. When stallions were not fed, leptin concentrations remained low. These results demonstrate that feeding time, and more specifically the insulin increase associated with a meal, not cortisol rhythm, drives the postprandial increase in plasma leptin concentrations in horses.

  19. Effect of intraportal and continuous intrajugular administration of insulin on feeding in sheep.

    Science.gov (United States)

    Deetz, L E; Wangsness, P J; Kavanaugh, J F; Griel, L C

    1980-10-01

    The effect of intraportal and intrajugular administration of insulin on feed intake and on glucose and insulin of jugular blood was studied. Ad libitum intake of four wethers was measured and jugular blood was sampled at various times after intraportal administration of the treatments and meal initiation. The treatments injected in the first experiment were saline, 2 mU, 4 mU and 6 mU insulin/kg body weight (BW), and in a second experiment were saline, 2 mU, 6 mU and 12 mU insulin/kg BW/minute infused over a 15-minute period. Feed intake was depressed only by 15-minute intraportal infusion of the 2 mU and 6 mU doses. Plasma insulin was elevated at 5 minutes after injection of 4 mU and 6 mU insulin/kg BW, and elevated at 5 and 15 minutes after 15-minute infusion of all three treatments; plasma glucose was not affected. Two additional experiments used four wethers in which jugular blood was sampled during a 24-hour intrajugular infusion of insulin. The combined treatments were saline, 0.02 mU, 0.2 mU, 2 mU and 6 mU insulin/kg BW/minute. The 6 mU dose stimulated feed intake, 2 mU increased plasma insulin and both 2 and 6 mU depressed plasma glucose. Thus, the site, timing and amount of exogeneous insulin administration may cause varying feed intake responses. The results are discussed with respect to a possible role of insulin in appetite control in sheep.

  20. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  1. Alternative routes of insulin delivery.

    Science.gov (United States)

    Krishnankutty, Ranjith K; Mathew, Aju; Sedimbi, Saikiran K; Suryanarayan, Shrikumar; Sanjeevi, Carani B

    2009-10-01

    Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications. Patient compliance has really been a major concern for this route of administration. Several alternative routes of administration are under consideration for effective glycemic control, including oral, inhaled, buccal, nasal, and patch routes. One of the approaches involving inhaled insulin has now reached the market. Several other candidates may reach the market in the near future, the promising one being oral insulin.

  2. Alternative routes of insulin delivery

    Institute of Scientific and Technical Information of China (English)

    Ranjith K. Krishnankutty; Aju Mathew; Saikiran K. Sedimbi; Shrikumar Suryanarayan; Carani B. Sanjeevi

    2009-01-01

    Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications. Patient compliance has really been a major concern for this route of administration. Several alternative routes of administration are under consideration for effective glycemic control, including oral, inhaled, buccal, nasal, and patch routes. One of the approaches involving inhaled insulin has now reached the market. Several other candidates may reach the market in the near future, the promising one being oral insulin.

  3. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper

    2015-01-01

    -chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Thus...

  4. Protection against the synaptic targeting and toxicity of Alzheimer's-associated Aβ oligomers by insulin mimetic chiro-inositols.

    Science.gov (United States)

    Pitt, Jason; Thorner, Michael; Brautigan, David; Larner, Joseph; Klein, William L

    2013-01-01

    Alzheimer's disease (AD) is a progressive dementia that correlates highly with synapse loss. This loss appears due to the synaptic accumulation of toxic Aβ oligomers (ADDLs), which damages synapse structure and function. Although it has been reported that oligomer binding and toxicity can be prevented by stimulation of neuronal insulin signaling with PPARγ agonists, these agonists have problematic side effects. We therefore investigated the therapeutic potential of chiro-inositols, insulin-sensitizing compounds safe for human consumption. Chiro-inositols have been studied extensively for treatment of diseases associated with peripheral insulin resistance, but their insulin mimetic function in memory-relevant central nervous system (CNS) cells is unknown. Here we demonstrate that mature cultures of hippocampal neurons respond to d-chiro-inositol (DCI), pinitol (3-O-methyl DCI), and the inositol glycan INS-2 (pinitol β-1-4 galactosamine) with increased phosphorylation in key upstream components in the insulin-signaling pathway (insulin receptor, insulin receptor substrate-1, and Akt). Consistent with insulin stimulation, DCI treatment promotes rapid withdrawal of dendritic insulin receptors. With respect to neuroprotection, DCI greatly enhances the ability of insulin to prevent ADDL-induced synapse damage (EC(50) of 90 nM). The mechanism comprises inhibition of oligomer binding at synapses and requires insulin/IGF signaling. DCI showed no effects on Aβ oligomerization. We propose that inositol glycans and DCI, a compound already established as safe for human consumption, have potential as AD therapeutics by protecting CNS synapses against Aβ oligomers through their insulin mimetic activity.

  5. Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng

    2015-09-08

    It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although Aβ levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower Aβ levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While Aβ can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of Aβ42 concentration. In contrast, ApoE4 bound more Aβ42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of Aβ42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this Aβ-mediated insulin signaling impairment.

  6. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2010-02-01

    When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

  7. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    S.G. Swinnen; M.P. Dain; D. Mauricio; J.H. Devries; J.B. Hoekstra; F. Holleman

    2010-01-01

    We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 di

  8. Action growth for AdS black holes

    Science.gov (United States)

    Cai, Rong-Gen; Ruan, Shan-Ming; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-09-01

    Recently a Complexity-Action (CA) duality conjecture has been proposed, which relates the quantum complexity of a holographic boundary state to the action of a Wheeler-DeWitt (WDW) patch in the anti-de Sitter (AdS) bulk. In this paper we further investigate the duality conjecture for stationary AdS black holes and derive some exact results for the growth rate of action within the Wheeler-DeWitt (WDW) patch at late time approximation, which is supposed to be dual to the growth rate of quantum complexity of holographic state. Based on the results from the general D-dimensional Reissner-Nordström (RN)-AdS black hole, rotating/charged Bañados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a universal formula for the action growth expressed in terms of some thermodynamical quantities associated with the outer and inner horizons of the AdS black holes. And we leave the conjecture unchanged that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  9. Complexity Growth for AdS Black Holes

    CERN Document Server

    Cai, Rong-Gen; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-01-01

    We further investigate the Complexity-Action (CA) duality conjecture for stationary anti de-Sitter (AdS) black holes and derive some exact results for the growth rate of action within Wheeler-DeWitt (WDW) patch at late time approximation, which is dual to the growth rate of quantum complexity of holographic state. Based on the results from the general $D$-dimensional Reissner-Nordstr\\"{o}m (RN)-AdS black hole, rotating/charged Ba\\~{n}ados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a new complexity bound but leave unchanged the conjecture that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  10. AdS_5 Black Holes with Fermionic Hair

    CERN Document Server

    Burrington, B A; Sabra, W A; Burrington, Benjamin A.; Liu, James T.

    2004-01-01

    The study of new BPS objects in AdS_5 has led to a deeper understanding of AdS/CFT. To help complete this picture, and to fully explore the consequences of the supersymmetry algebra, it is also important to obtain new solutions with bulk fermions turned on. In this paper we construct superpartners of the 1/2 BPS black hole in AdS_5 using a natural set of fermion zero modes. We demonstrate that these superpartners, carrying fermionic hair, have conserved charges differing from the original bosonic counterpart. To do so, we find the R-charge and dipole moment of the new system, as well as the mass and angular momentum, defined through the boundary stress tensor. The complete set of superpartners fits nicely into a chiral representation of AdS_5 supersymmetry, and the spinning solutions have the expected gyromagnetic ratio, g=1.

  11. Constructing the AdS dual of a Fermi liquid: AdS Black holes with Dirac hair

    CERN Document Server

    \\vCubrović, Mihailo; Schalm, Koenraad

    2010-01-01

    We provide new evidence that the holographic dual to a strongly coupled charged Fermi Liquid has a non-zero fermion density in the bulk. We show that the pole-strength of the stable quasiparticle characterizing the Fermi surface is encoded in the spatially averaged AdS probability density of a single normalizable fermion wavefunction in AdS. Recalling Migdal's theorem which relates the pole strength to the Fermi-Dirac characteristic discontinuity in the number density at $\\ome_F$, we conclude that the AdS dual of a Fermi liquid is described by occupied on-shell fermionic modes in AdS. Encoding the occupied levels in the total probability density of the fermion field directly, we show that an AdS Reissner-Nordstr\\"{o}m black hole in a theory with charged fermions has a critical temperature, at which the system undergoes a first-order transition to a black hole with a non-vanishing profile for the bulk fermion field. Thermodynamics and spectral analysis confirm that the solution with non-zero AdS fermion-profil...

  12. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

  13. Insulin signaling meets mitochondria in metabolism

    OpenAIRE

    Cheng, Zhiyong; Tseng, Yolanda; White, Morris F.

    2010-01-01

    Insulin controls nutrient and metabolic homeostasis via the IRS–PI3K–AKT signaling cascade that targets FOXO1 and mTOR. Mitochondria, as the prime metabolic platform, malfunction during insulin resistance in metabolic diseases. However, the molecular link between insulin resistance and mitochondrial dysfunction remains undefined. Here we review recent studies on insulin action and the mechanistic association with mitochondrial metabolism. These studies suggest that insulin signaling underpins...

  14. Bioavailability and variability of biphasic insulin mixtures

    DEFF Research Database (Denmark)

    Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik

    2012-01-01

    , the absorption kinetics for mixtures of insulins is described. This requires that the bioavailability of the different insulins is considered. A short review of insulin bioavailability and a description of the subcutaneous depot thus precede the presentation of possible mechanisms associated with subcutaneous...... mixtures. The results can be used in both the development of novel insulin products and in the planning of the treatment of insulin dependent diabetic patients....

  15. Different views of AEGIS / AD-6 Experiment (AD facility) AD-6

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    Different views of AEGIS / AD-6 Experiment (AD facility) in July of 2012. The visible parts are the positron accumulator (blue structures on top of of the antiproton extraction line) and the 5T magnet which traps the antiprotons.

  16. Global geometric properties of AdS space and the AdS/CFT correspondence

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Poisson kernels and relations between them for a massive scalar field in a unit ball Bn with Hua's metric and conformal flat metric are obtained by describing the Bn as a submanifold of an (n+1)-dimensional embedding space. Global geometric properties of the AdS space are discussed. We show that the(n+1)-dimensional AdS space AdSn+1 is isomorphic to RP1×Bn and boundary of the AdS is isomorphic to RP1×Sn-1. Bulk-boundary propagator and the AdS/CFT like correspondence are demonstrated based on these global geometric properties of the RP1×Bn.

  17. Insulin biosynthesis and diabetes mellitus.

    Science.gov (United States)

    Permutt, A; Chirgwin, J; Giddings, S; Kakita, K; Rotwein, P

    1981-10-01

    This review reports the use of recombinant DNA techniques in the study of the structure and regulation of expression of insulin genes in man and experimental animals. Insulin biosynthesis by pancreatic islet cells is predominantly regulated by change in plasma glucose concentration. Using a cell-free protein synthesizing system as an assay of functional proinsulin messenger RNA (mRNA), and hybridization analysis with a cloned DNA complementary to proinsulin mRNA, it has been determined that through changes in proinsulin mRNA levels. Insulin genes of the rat, chicken and human have been isolated and sequenced. The 5' ends of the genes have similar sequences suggesting areas important for regulation of transcription. There are two non-allelic insulin genes in the rat, but only one in chickens and humans. Intervening sequences, areas of DNA transcribed into precursor mRNA but which do not appear in mature mRNA, have been described within insulin genes. The insulin gene resides on chromosome 11 of humans as determined by DNA hybridization analysis of mouse human hybrid cells. The structure of the insulin gene in genomic DNA of humans has been analyzed in diabetics and non-diabetics. Insertions of DNA between 1500 and 3400 base pairs have been detected near the transcription initiation site in 65% of type II diabetics, and 25-30% of non-diabetics (this difference is significant at the p less than 0.001 level). Limitation of these insertions to this potential promotor region of the insulin gene suggests that they may alter gene expression in type II diabetes. These insertions of DNA may prove to be useful genetic markers for diabetes.

  18. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    Science.gov (United States)

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  19. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    CERN Document Server

    Evnin, Oleg

    2016-01-01

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  20. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Science.gov (United States)

    Ren, Jie

    2016-07-01

    Exact solutions to Einstein's equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution's appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  1. Entanglement entropy for free scalar fields in AdS

    CERN Document Server

    Sugishita, Sotaro

    2016-01-01

    We compute entanglement entropy for free massive scalar fields in anti-de Sitter (AdS) space. The entangling surface is a minimal surface whose boundary is a sphere at the boundary of AdS. The entropy can be evaluated from the thermal free energy of the fields on a topological black hole by using the replica method. In odd-dimensional AdS, exact expressions of the Renyi entropy S_n are obtained for arbitrary n. We also evaluate 1-loop corrections coming from the scalar fields to holographic entanglement entropy. Applying the results, we compute the leading difference of entanglement entropy between two holographic CFTs related by a renormalization group flow triggered by a double trace deformation. The difference is proportional to the shift of a central charge under the flow.

  2. Microstates at the boundary of AdS

    CERN Document Server

    Mathur, Samir D

    2011-01-01

    The bound states of the D1D5 brane system have a known gravitational description: flat asymptotics, an anti-de Sitter region, and a 'cap' ending the AdS region. We construct perturbations that correspond to the action of chiral algebra generators on Ramond ground states of D1D5 branes. Abstract arguments in the literature suggest that the perturbation should be pure gauge in the AdS region; our perturbation indeed has this structure, with the nontrivial deformation of the geometry occurring at the 'neck' between the AdS region and asymptotic infinity. This 'non-gauge' deformation is needed to provide the nonzero energy and momentum carried by the perturbation. We also suggest implications this structure may have for the majority of microstates which live at the cap.

  3. Revisiting the thermodynamic relations in AdS /CMT models

    Science.gov (United States)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2017-03-01

    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  4. Insulin Signaling and Glucose Uptake in the Soleus Muscle of 30-Month-Old Rats After Calorie Restriction With or Without Acute Exercise.

    Science.gov (United States)

    Wang, Haiyan; Sharma, Naveen; Arias, Edward B; Cartee, Gregory D

    2016-03-01

    Exercise and calorie restriction (CR) can each improve insulin sensitivity in older individuals, but benefits of combining these treatments on skeletal muscle insulin signaling and glucose uptake are poorly understood, especially in predominantly slow-twitch muscles (eg, soleus). Accordingly, our purpose was to determine independent and combined effects of prior acute exercise and CR (beginning at 14 weeks old) on insulin signaling and glucose uptake in insulin-stimulated soleus muscles of 30-month-old rats. CR alone (but not exercise alone) versus ad libitum sedentary controls induced greater insulin-stimulated glucose uptake. There was a main effect of diet (CR > ad libitum) for insulin-stimulated Akt(Ser473) and Akt(Thr308) phosphorylation. CR alone versus ad libitum sedentary increased Akt substrate of 160 kDa (AS160) Ser(588) phosphorylation and TBC1D1 Thr(596), but not AS160 Thr(642) phosphorylation or abundance of GLUT4, GLUT1, or hexokinase II proteins. Combined CR and exercise versus CR alone did not further increase insulin-stimulated glucose uptake although phosphorylation of Akt(Ser473), Akt(Thr308), TBC1D1(Thr596), and AMPK(Thr172) for the combined group exceeded values for CR and/or exercise alone. These results revealed that although the soleus was highly responsive to a CR-induced enhancement of insulin-stimulated glucose uptake, the exercise protocol did not elevate insulin-stimulated glucose uptake, either alone or when combined with CR.

  5. 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.

  6. Diffusion and Chaos from near AdS$_2$ horizons

    CERN Document Server

    Blake, Mike

    2016-01-01

    We calculate the thermal diffusivity $D = \\kappa/c_{\\rho}$ and butterfly velocity $v_B$ in holographic models that flow to AdS$_2 \\times R^{d}$ fixed points in the infra-red. We show that both these quantities are governed by the same irrelevant deformation of AdS$_2$ and hence establish a simple relationship between them. When this deformation corresponds to a universal dilaton mode of dimension $\\Delta = 2$ then this relationship is always given by $D = v_B^2/(2 \\pi T)$.

  7. An $xp$ model on $AdS_2$ spacetime

    OpenAIRE

    2012-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, whose absolute values are given by a harmonic oscillator spectrum, which in turn coincides with that of a massive Dirac fermion in AdS$_2$. We extend this result to generic $xp$ models which are shown to be equivalent to a massive Dirac fermion on spacetimes whose metric depend of the $xp$ Hamiltonian. Finally, we construct the generators of t...

  8. Mapping AdS to dS and back

    CERN Document Server

    Di Dato, Adriana

    2014-01-01

    We derive a map between Einstein spaces of positive and negative curvature. Starting from a space of positive curvature with some dimensions compactified on a sphere and analytically continuing the number of compact dimensions, we obtain a space of negative curvature with a compact hyperbolic subspace, and vice versa. Prime examples of such spaces are de Sitter and Anti-de Sitter space, as well as black hole spacetimes with (A)dS asymptotics and perturbed versions thereof, which play an important role in holography. This map extends work done by Caldarelli et.al., who map asymptotically AdS spaces to Ricci-flat ones. A remarkable result is that the boundary of asymptotically AdS spaces is mapped to a brane in the bulk of de Sitter, and perturbations near the AdS boundary are sourced by a stress tensor confined to this brane. We also calculate the Brown-York stress tensor for the perturbed AdS metric, which turns out to be the negative of the stress tensor on the de Sitter brane.

  9. Peripheral insulin sensitivity as modified by diet and exercise training.

    Science.gov (United States)

    Grimditch, G K; Barnard, R J; Hendricks, L; Weitzman, D

    1988-07-01

    To determine which component of a high-fat sucrose diet (HFS) caused insulin resistance and whether exercise training or fiber could prevent it, six dietary treatments were tested in rats: low-fat complex carbohydrate (LFCC); high-fat complex carbohydrate (HFCC); low-fat sucrose (LFS); high-fat sucrose (HFS); HFS plus fiber (HFS + F); and HFS plus exercise training (HFS + EX). After 10 wk rats were subjected to an intravenous glucose-tolerance test. The HFS and HFS + F groups developed glucose intolerance, as indicated by significantly greater areas under their glucose curves compared with the LFCC group's areas. The LFS, HFS, HFS + F, and HFS + EX groups developed insulin resistance, as indicated by significantly greater areas under their insulin curves compared with the LFCC and HFCC groups' areas. Either the presence of sucrose or the absence of complex carbohydrates, not high fat, was responsible for the insulin resistance and it was not improved by adding fiber to the diet or by exercise training.

  10. Insulin addition to swine semen diluted and cooled at 15 ºC

    Directory of Open Access Journals (Sweden)

    Evandro César Pereira Cunha

    2012-04-01

    Full Text Available The objective of this study was to evaluate the effect of adding different doses of insulin to swine semen processed and stored at 15 ºC. The experiment used sixteen ejaculates from four commercial breeding pigs, distributed in a randomized block design (ejaculate with split plot along time (0, 24, 48 and 72 hours of storage with four treatments (insulin levels - 0.0 4.0 8.0 and 12.0 IU per dose and 16 repetitions. The experimental unit was made of two insemination doses of 100 mL each, with 3×10(9 spermatozoids. Insulin used was NPH-human, added at the time of processing the doses. The addition of insulin did not affect motility, sperm viability, the percentage of abnormal cells, the osmotic resistance or the degradation rate of motility in 120 minutes. There was a linear decrease in semen quality over storage time, regardless of insulin levels. The addition of insulin at the mentioned concentrations does not influence the quality of insemination dose in pigs.

  11. Influence of intrajugular administration of insulin, glucagon and propionate on voluntary feed intake of sheep.

    Science.gov (United States)

    Deetz, L E; Wangsness, P J

    1981-08-01

    The effect of intrajugular injections of insulin, glucagon and propionate, administered singly and in combination, as possible peripheral feedbacks in the control of feed intake in wethers was studied. A complete mixed diet (25% chopped hay: 75% cracked corn) was fed ad libitum. The treatments were saline, 6 mU insulin/kg body weight (BW), 9 ng glucagon/kg BW and 1.3 mg propionate/kg BW. In Exp. 1, five wethers were given the treatments at the beginning of each spontaneous meal over a 24-hr period, and total daily feed intakes were measured. The average number of injections per sheep for a 24-hr period was eight. In Exp. 2, the effects of the treatments on plasma concentrations of insulin, glucagon, propionate and glucose at 15, 30, 60 and 120 min after injection were measured in six other wethers. In Exp. 1, insulin (P less than .01), glucagon (P less than .01), insulin plus propionate (P less than .05) and glucagon plus propionate (P less than .05) decreased 24-hr feed intake by 18.5, 15.8, 11.0 and 11.8%, respectively, compared to the saline control. In Exp. 2, plasma insulin concentrations were increased (P less than .05) at 15 min after administration of insulin and insulin plus propionate, to 2.0 and 2.1 times the preinjection levels, respectively. Glucagon concentrations in plasma were increased (P less than .01) at 15 min after the injection of glucagon, to 2.0 times the pretreatment values. Insulin and glucagon concentrations in plasma were increased only slightly (P less than .10) after administration of glucagon plus propionate. No treatments affected glucose or propionate concentrations in the plasma. Increases in plasma concentrations of insulin, glucagon and propionate may interact directly or initiate other mechanisms involved in the short-term control of feed intake by sheep on a concentrate diet.

  12. Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhou; (张舟); TANG; Yuehua; (唐月华); YAO; Shiyin; (姚矢音); ZHU; Shangquan; (朱尚权); FENG; Youmin; (冯佑民)

    2003-01-01

    Blood glucose lowering assay proved that [B16Ala]insulin and [B26Ala]insulin exhibit potency of acute blood glucose lowering in normal pigs, which demonstrates that they are fast- acting insulin. Single-chain precursor of [B16Ala]insulin and [B26Ala]insulin is [B16Ala]PIP and [B26Ala]PIP, respectively, which are suitable for gene expression. Secretory expression level of the precursors in methylotrophic yeast Pichia pastoris was quite high, 650 mg/L and 130 mg/L, respectively. In vivo biological assay showed that the two fast-acting insulins have full or nearly full biological activity. So both [B16Ala]insulin and [B26Ala]insulin can be well developed as fast-acting insulin for clinic use.

  13. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  14. Observation on the effect of Glargine combined with Metformin and/or pioglitazone in treatment for the newly diagnosed type 2 diabetes%甘精胰岛素联合二甲双胍或/和吡格列酮治疗初诊2型糖尿病疗效观察

    Institute of Scientific and Technical Information of China (English)

    全会标; 高勇义

    2012-01-01

    OBJECTIVE To compare the clinical effects and safety of treating newly diagnosed type 2diabetes patients by combining Glargine with Metformin or/and pioglitazone. METHODS 98 cases with newly diagnosed type 2 diabetes, who had poorly controlled blood glucose with Metformin at least four weeks, were randomly divided into three groups. Glargine plus Metformin were used in group A. Glargine plus pioglitazone were used in group B, and glargine plus pioglitazone and metformin were used in Group C. All three groups were given a 12-week follow-up. RESULTS FPG of patients was all up to the standard, and 2hPG and HbAlc levels were lower in the patients after treatment (P 0.05). In all three groups, no severe hypoglycemia occurred. CONCLUSION The method of combining Glargine with Metformin and pioglitazone could effectively control blood sugar of the newly diagnosed type 2 diabetes patients. Moreover, the incidence of low blood sugar was lower.lt would be the ideal method to treat newly diagnosed type 2 diabetes patients considering the general safety and effectiveness.%目的 比较甘精胰岛素联合二甲双胍或/和吡格列酮治疗初诊2型糖尿病(T2DM)的疗效及安全性.方法 初诊T2DM先单用二甲双胍(1.0 g/d)治疗4周,血糖控制不佳的98例患者随机分为3组.A组:二甲双胍+甘精胰岛素,B组:吡格列酮+甘精胰岛素,C组:二甲双胍+吡格列酮+甘精胰岛素,治疗随访12周.结果 12周后3组患者的空腹血糖(FPG)全部达标,餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)均比治疗前明显降低,A、B两组HbA1c部分达标,C组HbA1c达标(P<0.05).C组疗效优于A、B组,FPG达标所需时间最短,日胰岛素用量最少.3组低血糖发生率均<3.5%,无严重低血糖,差异无统计学意义(P>0.05).结论 甘精胰岛素联合二甲双胍或/和吡格列酮均能较好地控制血糖,低血糖发生率低,三药联合疗效优于二药联合,安全有效是初诊T2DM理想的治疗方案.

  15. Penrose inequality for asymptotically AdS spaces

    Energy Technology Data Exchange (ETDEWEB)

    Itkin, Igor [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Oz, Yaron, E-mail: yaronoz@post.tau.ac.il [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2012-02-28

    In general relativity, the Penrose inequality relates the mass and the entropy associated with a gravitational background. If the inequality is violated by an initial Cauchy data, it suggests a creation of a naked singularity, thus providing means to consider the cosmic censorship hypothesis. We propose a general form of Penrose inequality for asymptotically locally AdS spaces.

  16. Internet Advertising. Google AdWords versus Facebook Ads

    Directory of Open Access Journals (Sweden)

    Paul PAŞCU

    2014-05-01

    Full Text Available This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  17. Insulin resistance: β-arrestin development

    Institute of Scientific and Technical Information of China (English)

    Joseph T Rodgers; Pere Puigserver

    2009-01-01

    @@ Insulin resistance is simply the in-ability of insulin to elicit a physiologic response. While insulin resistance is most commonly associated with the pathogenesis of metabolic disorders such as type II diabetes and obesity, it is also a predisposing factor to a number of other diseases such as cancer and car-diovascular disease . There are just as many theories as to the cause of insulin resistance as there are insulin signal-ing molecules and it is very unclear as to which are the actual molecular mechanisms of insulin resistance in diseased states.

  18. Predicting AD conversion: comparison between prodromal AD guidelines and computer assisted PredictAD tool.

    Directory of Open Access Journals (Sweden)

    Yawu Liu

    Full Text Available To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA on MRI and CSF biomarkers.Altogether 391 MCI cases (158 AD converters were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1-42 and Tau. Using baseline data, the status of MCI patients (AD or MCI three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1 clinical criteria for episodic memory loss of the hippocampal type, 2 visual MTA, 3 positive CSF markers, 4 their combinations, and 5 when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.The PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71% in predicting the AD diagnosis. The corresponding number for a clinician's prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%. Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037.With the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.

  19. AdS5 backgrounds with 24 supersymmetries

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2016-06-01

    We prove a non-existence theorem for smooth AdS 5 solutions with connected, compact without boundary internal space that preserve strictly 24 supersymmetries. In particular, we show that D = 11 supergravity does not admit such solutions, and that all such solutions of IIB supergravity are locally isometric to the AdS 5 × S 5 maximally supersymmetric background. Furthermore, we prove that (massive) IIA supergravity also does not admit such solutions, provided that the homogeneity conjecture for massive IIA supergravity is valid. In the context of AdS/CFT these results imply that if gravitational duals for strictly mathcal{N}=3 superconformal theories in 4-dimensions exist, they are either singular or their internal spaces are not compact.

  20. Coset construction of AdS particle dynamics

    CERN Document Server

    Heinze, Martin; Megrelidze, Luka

    2016-01-01

    We analyze dynamics of the AdS$_{N+1}$ particle realized on the coset SO$(2,N)/$SO$(1,N)$. Hamiltonian reduction provides the physical phase space in terms of the coadjoint orbit obtained by boosting a timelike element of ${\\frak so}(2,N)$. We show equivalence of this approach to geometric quantization and to the SO$(N)$ covariant oscillator description, for which the boost generators entail a complicated operator ordering. As an alternative scheme, we introduce dual oscillator variables and derive their algebra at the classical and the quantum level. This simplifies the calculations of the commutators for the boost generators and leads to unitary irreducible representations of ${\\frak so}(2,N)$ for all admissible values of the mass parameter. We furthermore discuss a SO$(N)$ covariant supersymmetric extensions of the oscillator quantization, with its realization for superparticles in AdS$_2$ and AdS$_3$ given by recent works.

  1. Clinical use of the co-formulation of insulin degludec and insulin aspart

    DEFF Research Database (Denmark)

    Kumar, A; Awata, T; Bain, S C;

    2016-01-01

    AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage...... as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting...... (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...

  2. Study on interaction of mangiferin to insulin and glucagon in ternary system

    Science.gov (United States)

    Lin, Hui; Chen, Rui; Liu, Xiaoyan; Sheng, Fenling; Zhang, Haixia

    2010-05-01

    The binding of mangiferin to insulin and glucagon was investigated in the presence and absence of another Peptide by optical spectroscopy. Fluorescence titration experiments revealed that mangiferin quenched the intrinsic fluorescence of insulin and glucagon by static quenching. The ratios of binding constants of glucagon-mangiferin to insulin-mangiferin at different temperatures were calculated in "pure" and ternary system, respectively. The results indicated that the Peptides were competitive with each other to act on mangiferin. Values of the thermodynamic parameters and the experiments of pH effect proved that the key interacting forces between mangiferin and the Peptides were hydrophobic interaction. In addition, UV-vis absorption, synchronous fluorescence and Fourier transform infrared measurements showed that the conformation of insulin and glucagon were changed after adding mangiferin.

  3. Oral insulin--a perspective.

    Science.gov (United States)

    Raj, N K Kavitha; Sharma, Chandra P

    2003-01-01

    Diabetes mellitus is generally controlled quite well with the administration of oral medications or by the use of insulin injections. The current practice is the use of one or more doses, intermediate or long acting insulin per day. Oral insulin is a promising yet experimental method providing tight glycemic control for patients with diabetes. A biologically adhesive delivery systems offer important advantage over conventional drug delivery systems. The engineered polymer microspheres made of erodable polymer display strong adhesive interactions with gastrointestinal mucus and cellular lining can traverse both the mucosal epithelium and the follicle associated epithelium covering the lymphoid tissue of Peyer's patches. Alginate, a natural polymer recovered from seaweed is being developed as a nanoparticle for the delivery of insulin without being destroyed in the stomach. Alginate is in fact finding application in biotechnology industry as thickening agent, a gelling agent and a colloid stabilizer. Alginate has in addition, several other properties that have enabled it to be used as a matrix for entrapment and for the delivery of a variety of proteins such as insulin and cells. These properties include: a relatively inert aqueous environment within the matrix; a mild room temperature encapsulation process free of organic solvents; a high gel porosity which allows for high diffusion rates of macromolecules; the ability to control this porosity with simple coating procedures and dissolution and biodegradation of the system under normal physiological conditions.

  4. Engineering of insulin receptor isoform-selective insulin analogues.

    Directory of Open Access Journals (Sweden)

    Tine Glendorf

    Full Text Available BACKGROUND: The insulin receptor (IR exists in two isoforms, A and B, and the isoform expression pattern is tissue-specific. The C-terminus of the insulin B chain is important for receptor binding and has been shown to contact the IR just adjacent to the region where the A and B isoforms differ. The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues. METHODOLOGY/PRINCIPAL FINDINGS: Insulin analogue libraries were constructed by total amino acid scanning mutagenesis. The relative binding affinities for the A and B isoform of the IR were determined by competition assays using scintillation proximity assay technology. Structural information was obtained by X-ray crystallography. Introduction of B25A or B25N mutations resulted in analogues with a 2-fold preference for the B compared to the A isoform, whereas the opposite was observed with a B25Y substitution. An acidic amino acid residue at position B27 caused an additional 2-fold selective increase in affinity for the receptor B isoform for analogues bearing a B25N mutation. Furthermore, the combination of B25H with either B27D or B27E also resulted in B isoform-preferential analogues (2-fold preference even though the corresponding single mutation analogues displayed no differences in relative isoform binding affinity. CONCLUSIONS/SIGNIFICANCE: We have discovered a new class of IR isoform-selective insulin analogues with 2-4-fold differences in relative binding affinities for either the A or the B isoform of the IR compared to human insulin. Our results demonstrate that a mutation at position B25 alone or in combination with a mutation at position B27 in the insulin molecule confers IR isoform selectivity. Isoform-preferential analogues may provide new opportunities for developing insulin analogues with improved clinical benefits.

  5. Quality of Life in Type 2 Diabetes Mellitus Patients Requiring Insulin Treatment in Buenos Aires, Argentina: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Andres Pichon-Riviere

    2015-07-01

    Full Text Available Background Decision-makers have begun to recognize Health-Related Quality of Life (HRQoL as an important and measurable outcome of healthcare interventions; and HRQoL data is increasingly being used by policy-makers to prioritize health resources. Our objective was to measure HRQoL in a group of Type 2 Diabetes Mellitus (T2DM patients receiving insulin treatment in Buenos Aires, Argentina. Methods We conducted a cross-sectional study of patients with T2DM over 21 years of age, treated with either Neutral Protamine Hagedorn (NPH insulin or Insulin Glargine (IG, who had not changed their baseline schedule in the last 6 months. The recruitment was during 2006–7 in nine private diabetes specialists’ offices in Buenos Aires, Argentina. A standardized diabetes-specific HRQoL questionnaire, the Audit of Diabetes Dependent Quality of Life (ADDQoL, was used. Results A total of 183 patients were included (93 receiving NPH and 90 receiving IG. The mean QoL score was: 0.98 (SD: 0.89 and the diabetes specific QoL was: -1.49 (SD: 0.90. T2DM had a negative impact on HRQoL with a mean Average Weighted Impact (AWI score on QoL of -1.77 (SD: 1.58. The greatest negative impact was observed for domains: ‘worries about the future’, ‘freedom to eat’, ‘living conditions’, ‘sex life’, and ‘family life’. The mean AWI score was -1.71 (SD: 1.48 in patients treated with IG and -1.85 (SD: 1.68 in patients receiving NPH, this difference was not statistically significant. Conclusion The ADDQoL questionnaire is a tool that can be used in Argentina to measure the QoL of patients with diabetes when evaluating diabetes care programs. The scores of QoL in our selected population did not differ from those reported in high-income countries. We expect that the results of this study will increase healthcare providers’ awareness of patients’ perceived QoL and help to overcome the barriers that delay insulin treatment; mainly clinical inertia and patient

  6. Sub-AdS Scale Locality in AdS$_3$/CFT$_2$

    CERN Document Server

    Belin, Alexandre; Jefferson, Robert A; Kabir, Laurens

    2016-01-01

    We investigate sub-AdS scale locality in a weakly coupled toy model of the AdS$_3$/CFT$_2$ correspondence. We find that this simple model has the correct density of states at low and high energies to be dual to Einstein gravity coupled to matter in AdS$_3$. Bulk correlation functions also have the correct behavior at leading order in the large $N$ expansion, but non-local effects emerge at order $1/N$. Our analysis leads to the conjecture that any large $N$ CFT$_2$ that is modular invariant and has the right low-energy density of states is dual to a gravitational theory with sub-AdS scale locality.

  7. Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis.

    Science.gov (United States)

    Hayashi, Hiroko; Yamaza, Haruyoshi; Komatsu, Toshimitsu; Park, Seongjoon; Chiba, Takuya; Higami, Yoshikazu; Nagayasu, Takeshi; Shimokawa, Isao

    2008-09-01

    Calorie restriction (CR) may modulate insulin signaling in response to energy intake through suppression of the growth hormone (GH)-IGF-1 axis. We investigated the glucose-stimulated serum insulin response and subsequent alterations in insulin receptor (IR), Akt, and FoxO1 in the rat liver and quadriceps femoris muscle (QFM). Nine-month-old wild-type (W) male Wistar rats fed ad libitum (AL) or a 30% CR diet initiated at 6 weeks of age and GH-suppressed transgenic (Tg) rats fed AL were killed 15 min after intraperitoneal injection of glucose or saline. In W-AL rats, the serum insulin concentration was elevated by glucose injection. Concomitantly, the phosphorylated (p)-IR and p-Akt levels were increased in both tissues. The active FoxO1 level was decreased in the liver, but not significantly in the QFM. In W-CR and Tg-AL rats, the serum insulin response was lower, and no significant changes were noted for the p-IR, p-Akt, or active FoxO1 levels in the liver. In the QFM, the p-Akt level was increased in W-CR and Tg-AL rats with an insignificant elevation of p-IR levels. The phenotypic similarity of W-CR and Tg-AL rats suggest that CR minimizes activation of insulin signaling in response to energy intake mostly through the GH-IGF-1 axis.

  8. Ultraviolet asymptotics for quasiperiodic AdS_4 perturbations

    CERN Document Server

    Craps, Ben; Jai-akson, Puttarak; Vanhoof, Joris

    2015-01-01

    Spherically symmetric perturbations in AdS-scalar field systems of small amplitude epsilon approximately periodic on time scales of order 1/epsilon^2 (in the sense that no significant transfer of energy between the AdS normal modes occurs) have played an important role in considerations of AdS stability. They are seen as anchors of stability islands where collapse of small perturbations to black holes does not occur. (This collapse, if it happens, typically develops on time scales of the order 1/epsilon^2.) We construct an analytic treatment of the frequency spectra of such quasiperiodic perturbations, paying special attention to the large frequency asymptotics. For the case of a self-interacting phi^4 scalar field in a non-dynamical AdS background, we arrive at a fairly complete analytic picture involving quasiperiodic spectra with an exponential suppression modulated by a power law at large mode numbers. For the case of dynamical gravity, the structure of the large frequency asymptotics is more complicated....

  9. Obesity, inflammation, and insulin resistance

    Directory of Open Access Journals (Sweden)

    Luana Mota Martins

    2014-12-01

    Full Text Available White adipose tissue (WAT is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT.

  10. Radioreceptor assay method for insulin

    Energy Technology Data Exchange (ETDEWEB)

    Mori, K.F.; Wood, R.J. (Bureau of Drug Research, Health and Welfare Canada, Ottawa, Ontario. Health Protection Branch)

    1984-01-01

    A sensitive practical radioreceptor assay method for pharmaceutical insulin products has been developed with partially purified rat liver plasma membranes and the optimal conditions under which the best overall assay performance is obtainable have been defined. Intra- and inter-assay variations of the method averaged 7.3 and 12.2% of the man, respectively, when expressed as the coefficient of variation. Potency estimates of an insulin product obtained with the proposed method correlated well with those determined by the mouse convulsion bioassay method. Liver membranes prepared according to the method could be stored for up to ten weeks at 4/sup 0/C and for 6 months or more at -18/sup 0/C without losing insulin-binding ability.

  11. Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model.

    Science.gov (United States)

    Lin, Fangju; Jia, Jianping; Qin, Wei

    2014-11-12

    The β-amyloid (Aβ) oligomer rather than fibrillar Aβ has become the important focus of recent studies on the pathogenesis of Alzheimer's disease (AD). Insulin signaling plays important roles in cognitive disease, such as AD. However, in-vivo evidence for the link between central insulin signaling and the Aβ oligomer are lacking, and the mechanisms underlying the effect of central insulin signaling on AD are still elusive. Our team has established the Presenilin-1 Val97Leu mutant transgenic (PS1V97L) AD mouse model with the intraneuronal Aβ oligomer as the potential initiator for other pathologies, but without extracellular amyloid plaque formation. Using this model, we investigated the roles of disturbed central insulin signaling induced by intracerebroventricular injection of streptozotocin (STZ) in the progression of AD. We observed that PS1V97L mice after intracerebroventricular injection of STZ showed increased Aβ oligomer accumulation and aggravated spatial learning and memory deficit in the absence of diabetes symptoms. Furthermore, STZ administration inhibited the activation of the insulin receptor and enhanced the activation of c-Jun NH2-terminal kinase, which was accompanied by increased production of carboxy-terminal fragments from the amyloid precursor protein, in the brain of PS1V97L mice. Overall, our study provided in-vivo evidence for a role of central insulin signaling in AD progression.

  12. Kolmogorov-Zakharov spectrum in AdS gravitational collapse.

    Science.gov (United States)

    de Oliveira, H P; Pando Zayas, Leopoldo A; Rodrigues, E L

    2013-08-01

    We study black hole formation during the gravitational collapse of a massless scalar field in asymptotically D-dimensional anti-de Sitter AdS(D) spacetimes for D = 4, 5. We conclude that spherically symmetric gravitational collapse in asymptotically AdS spaces is turbulent and characterized by a Kolmogorov-Zakharov spectrum. Namely, we find that after an initial period of weakly nonlinear evolution, there is a regime where the power spectrum of the Ricci scalar evolves as ω(-s) with the frequency, ω, and s ≈ 1.7 ± 0.1.

  13. Insulin signaling meets mitochondria in metabolism.

    Science.gov (United States)

    Cheng, Zhiyong; Tseng, Yolanda; White, Morris F

    2010-10-01

    Insulin controls nutrient and metabolic homeostasis via the IRS-PI3K-AKT signaling cascade that targets FOXO1 and mTOR. Mitochondria, as the prime metabolic platform, malfunction during insulin resistance in metabolic diseases. However, the molecular link between insulin resistance and mitochondrial dysfunction remains undefined. Here we review recent studies on insulin action and the mechanistic association with mitochondrial metabolism. These studies suggest that insulin signaling underpins mitochondrial electron transport chain integrity and activity by suppressing FOXO1/HMOX1 and maintaining the NAD(+)/NADH ratio, the mediator of the SIRT1/PGC1α pathway for mitochondrial biogenesis and function. Mitochondria generate moderately reactive oxygen species (ROS) and enhance insulin sensitivity upon redox regulation of protein tyrosine phosphatase and insulin receptor. However, chronic exposure to high ROS levels could alter mitochondrial function and thereby cause insulin resistance.

  14. Insulin requirements in type 1 diabetic pregnancy

    DEFF Research Database (Denmark)

    Callesen, Nicoline; Ringholm, Lene; Stage, Edna;

    2012-01-01

    To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy.......To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy....

  15. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

  16. Insulin receptor what role in breast cancer?

    Science.gov (United States)

    Papa, V; Costantino, A; Belfiore, A

    1997-10-01

    It is commonly believed that the insulin receptor mainly mediates the metabolic effects of insulin, whereas the closely related IGF-I receptor is considered a major factor for the regulation of cell proliferation. Experimental and epidemiological evidence indicates, however, that insulin and insulin receptors may play an important role in breast cancer. This article reviews evidence indicating that (a) insulin receptors are overexpressed in human breast cancer, (b) insulin stimulates growth in breast cancer cells, (c) cells transfected with human insulin receptor may acquire a ligand-dependent transformed phenotype, and (d) breast cancer is associated with insulin resistance and hyperinsulinemia. These findings may open new possibilities in breast cancer prevention, prognosis assessment, and therapy. (Trends Endocrinol Metab 1997; 8:306-312). (c) 1997, Elsevier Science Inc.

  17. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

  18. Comparison of metformin and insulin versus insulin alone for type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn;

    2012-01-01

    To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes.......To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes....

  19. Redox regulation of insulin degradation by insulin-degrading enzyme.

    Directory of Open Access Journals (Sweden)

    Crystal M Cordes

    Full Text Available Insulin-degrading enzyme (IDE is a thiol sensitive peptidase that degrades insulin and amyloid β, and has been linked to type 2 diabetes mellitus and Alzheimer's disease. We examined the thiol sensitivity of IDE using S-nitrosoglutathione, reduced glutathione, and oxidized glutathione to distinguish the effects of nitric oxide from that of the redox state. The in vitro activity of IDE was studied using either partially purified cytosolic enzyme from male Sprague-Dawley rats, or purified rat recombinant enzyme. We confirm that nitric oxide inhibits the degrading activity of IDE, and that it affects proteasome activity through this interaction with IDE, but does not affect the proteasome directly. Oxidized glutathione inhibits IDE through glutathionylation, which was reversible by dithiothreitol but not by ascorbic acid. Reduced glutathione had no effect on IDE, but reacted with partially degraded insulin to disrupt its disulfide bonds and accelerate its breakdown to trichloroacetic acid soluble fragments. Our results demonstrate the sensitivity of insulin degradation by IDE to the redox environment and suggest another mechanism by which the cell's oxidation state may contribute to the development of, and the link between, type 2 diabetes and Alzheimer's disease.

  20. Patients with psoriasis are insulin resistant

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesized that systemic inflammation causes insulin resistance. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies...... no 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...

  1. Thermodynamics of Einstein-Proca AdS Black Holes

    CERN Document Server

    Liu, Hai-Shan; Pope, C N

    2014-01-01

    We study static spherically-symmetric solutions of the Einstein-Proca equations in the presence of a negative cosmological constant. We show that the theory admits solutions describing both black holes and also solitons in an asymptotically AdS background. Interesting subtleties can arise in the computation of the mass of the solutions and also in the derivation of the first law of thermodynamics. We make use of holographic renormalisation in order to calculate the mass, even in cases where the solutions have a rather slow approach to the asymptotic AdS geometry. By using the procedure developed by Wald, we derive the first law of thermodynamics for the black hole and soliton solutions. This includes a non-trivial contribution associated with the Proca "charge." The solutions cannot be found analytically, and so we make use of numerical integration techniques to demonstrate their existence.

  2. Universal isolation in the AdS landscape

    CERN Document Server

    Danielsson, U H; Vargas, S C

    2016-01-01

    We study the universal conditions for quantum non-perturbative stability against bubble nucleation for pertubatively stable AdS vacua based on positive energy theorems. We also compare our analysis with the pre-existing ones in the literature carried out within the thin-wall approximation. The aforementioned criterion is then tested in two explicit examples describing massive type IIA string theory compactified on $S^3$ and $S^3\\,\\times\\,S^3$, respectively. The AdS landscape of both classes of compactifications is known to consist of a set of isolated points. The main result is that all critical points respecting the Breitenlohner-Freedaman (BF) bound also turn out be stable at a non-perturbative level. Finally, we speculate on the possible universal features that may be extracted from the above specific examples.

  3. Perturbative entanglement thermodynamics for AdS spacetime: Renormalization

    CERN Document Server

    Mishra, Rohit

    2015-01-01

    We study the effect of charged excitations in the AdS spacetime on the first law of entanglement thermodynamics. It is found that `boosted' AdS black holes give rise to a more general form of first law which includes chemical potential and charge density. To obtain this result we have to resort to a second order perturbative calculation of entanglement entropy for small size subsystems. At first order the form of entanglement law remains unchanged even in the presence of charged excitations. But the thermodynamic quantities have to be appropriately `renormalized' at the second order due to the corrections. We work in the perturbative regime where $T_{thermal}\\ll T_E$.

  4. The Mixed Phase of Charged AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Piyabut Burikham

    2016-01-01

    Full Text Available We study the mixed phase of charged AdS black hole and radiation when the total energy is fixed below the threshold to produce a stable charged black hole branch. The coexistence conditions for the charged AdS black hole and radiation are derived for the generic case when radiation particles carry charge. The phase diagram of the mixed phase is demonstrated for both fixed potential and charge ensemble. In the dual gauge picture, they correspond to the mixed phase of quark-gluon plasma (QGP and hadron gas in the fixed chemical potential and density ensemble, respectively. In the nuclei and heavy-ion collisions at intermediate energies, the mixed phase of exotic QGP and hadron gas could be produced. The mixed phase will condense and evaporate into the hadron gas as the fireball expands.

  5. Note on classical string dynamics on AdS3

    Science.gov (United States)

    Bañados, Máximo; Ritz, Adam

    1999-12-01

    We consider bosonic strings propagating on Euclidean anti-de Sitter space (AdS3), and study in particular the realization of various worldsheet symmetries. We give a proper definition for the Brown-Henneaux asymptotic target space symmetry, when acting on the string action, and derive the Giveon-Kutasov-Seiberg worldsheet contour integral representation simply by using Noether's theorem. We show that making identifications in the target space is equivalent to the insertion of an (exponentiated) graviton vertex operator carrying the corresponding charge. Finally, we point out an interesting relation between 3D gravity and the dynamics of the worldsheet on AdS3. Both theories are described by an SL(2,C)/SU(2) Wess-Zumino-Witten (WZW) model, and we prove that the reduction conditions determined on one hand by worldsheet diffeomorphism invariance, and on the other by the Brown-Henneaux boundary conditions, are the same.

  6. Observing quantum gravity in asymptotically AdS space

    Science.gov (United States)

    Emelyanov, Slava

    2015-12-01

    The question is studied of whether an observer can discover quantum gravity in the semiclassical regime. It is shown that it is indeed possible to probe a certain quantum gravity effect by employing an appropriately designed detector. The effect is related to the possibility of having topologically inequivalent geometries in the path-integral approach at the same time. A conformal field theory (CFT) state which is expected to describe the eternal anti-de Sitter (AdS) black hole in the large-N limit is discussed. It is argued under certain assumptions that the black hole boundary should be merely a patch of the entire AdS boundary. This leads then to a conclusion that that CFT state is the ordinary CFT vacuum restricted to that patch. If existent, the bulk CFT operators can behave as the ordinary semiclassical quantum field theory in the large-N limit in the weak sense.

  7. Universal isolation in the AdS landscape

    Science.gov (United States)

    Danielsson, U. H.; Dibitetto, G.; Vargas, S. C.

    2016-12-01

    We study the universal conditions for quantum nonperturbative stability against bubble nucleation for pertubatively stable AdS vacua based on positive energy theorems. We also compare our analysis with the preexisting ones in the literature carried out within the thin-wall approximation. The aforementioned criterion is then tested in two explicit examples describing massive type IIA string theory compactified on S3 and S3×S3, respectively. The AdS landscape of both classes of compactifications is known to consist of a set of isolated points. The main result is that all critical points respecting the Breitenlohner-Freedman (BF) bound also turn out be stable at a nonperturbative level. Finally, we speculate on the possible universal features that may be extracted from the above specific examples.

  8. Smoothed Transitions in Higher Spin AdS Gravity

    CERN Document Server

    Banerjee, Shamik; Hellerman, Simeon; Hijano, Eliot; Lepage-Jutier, Arnaud; Maloney, Alexander; Shenker, Stephen

    2012-01-01

    We consider CFTs conjectured to be dual to higher spin theories of gravity in AdS_3 and AdS_4. Two dimensional CFTs with W_N symmetry are considered in the lambda=0 (k --> infinity) limit, where they are conjectured to be described by continuous orbifolds. The torus partition function is computed, using reasonable assumptions, and equals that of a free field theory. We find no phase transition at temperatures of order one; the usual Hawking-Page phase transition is removed by the highly degenerate light states associated with conical defect states in the bulk. Three dimensional Chern-Simons-matter CFTs with vector-like matter are considered on T^3, where the dynamics is described by an effective theory for the eigenvalues of the holonomies. Likewise, we find no evidence for a Hawking-Page phase transition at large level k.

  9. N=2 supersymmetric sigma-models in AdS

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We construct the most general N=2 supersymmetric nonlinear sigma-model in four-dimensional anti-de Sitter (AdS) space in terms of N=1 chiral superfields. The target space is shown to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field. A remarkable property of the sigma-model constructed is that the algebra of OSp(2|4) transformations is closed off the mass shell.

  10. Insulin degludec/insulin aspart is the first co-formulation of basal and prandial insulin analogues

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-12-01

    Full Text Available Achievement of glycemic control is the major therapeutic aim to prevent or delay the onset and progression of diabetes related complications. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. The aim for insulin therapy is to mimic the physiological profile of insulin secretion seen in nondiabetic patients. Development of the insulin analogs has offered new opportunities in the diabetes management to achieve greater safety and tolerability of diabetes treatment. Insulin degludec/insulin aspart(IDegAsp (Ryzodeg®, Novo Nordisk, Denmark is the first soluble co-formulation of 70% ultra-long acting insulin degludec and 30% rapid-acting prandial insulin aspart, providing both basal insulin coverage and a prandial insulin bolus in a single injection. This review discusses data regarding the efficacy, safety, tolerability and clinical benefits of IDegAsp. According to the clinical development program IDegAspprovides an achievement of similar glycemic control with superiority in lowering FPG with using less number of injections and lower daily insulin dose, and also associated with numerically lower rates of confirmed and nocturnal confirmed hypoglycaemia in comparison with premixed or basal insulin analogues, as well as a basal component for basal–bolus therapy with supplementary mealtime insulin aspart.Trial results suggest that IDegAspQD or BID maybe an appropriate and reasonable option for initiating insulin therapy in type 1 and type 2 diabetic patients inadequately controlled on maximal doses of oral antidiabetic drugs,and also a simple alternative to basal–bolus treatment in patients who require intensification of insulin therapy, especially when adherence to more complex regimens is challenging.

  11. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.;

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  12. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

  13. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Rastegar Hoseini

    2016-04-01

    Full Text Available Background and Aim: Type 2 diabetes mellitus (T2DM and vitamin D deficiency are both too common during menopause. Since the effect of different doses of vitamin D supplements on blood sugar, insulin concentration  and insulin resistance are unknown, the present study aimed at investigating the effects of different doses of the vitamin D supplements on visceral fat, blood sugar, insulin concentration,  and insulin resistance in ovariectomized rats. Materials and Methods: In this randomized experimental study, 32 female Wistar rats were divided into 4 equal groups  as follows: three groups . that received vitamin D supplements (high, moderate, and low dose and one control group. After 8 weeks of different doses of vitamin D supplementation plasma concentration of glucose, insulin and HOMA-IR were measured  in the three groups. The obtained data  was statistically analyzed by means of dependent t-test and ANOVA . at the significance level of P<0.05. Results: After a period of eight-week  intervention, body weight, BMI, waist circumference, visceral fat, insulin, blood glucose and HOMA-IR at high, moderate, and low doses of vitamin D supplementation were significantly lower than those in the control group (P<0.05. High dose of vitamin D compared with moderate and low doses significantly caused reduction in insulin, blood glucose, and HOMA-IR (P<0.001 for all three variables. Conclusion: The findings of the current study showed that a high dose of vitamin D causes significant improvements in FPG, insulin, and insulin resistance  evaluated by HOMA-IR. It was also found that adding vitamin D supplements can improve glucose control in menopause model of rats.

  14. [A21-Asparaginimide] insulin. Saponification of insulin hexamethyl ester, I.

    Science.gov (United States)

    Gattner, H G; Schmitt, E W

    1977-01-01

    [Asn A21]Insulin is formed as the main product during alkaline saponification of insulin hexamethyl ester. Purification was achieved by gel chromatography followed by ion-exchange chromatography on carboxymethyl cellulose at pH 4 or by preparative isoelectric focusing in a granulated gel over a narrow pH range. Two main products could be isolated. One of them showed the electrophoretic behaviour of insulin (A), whilst the other corresponded to insulin with a blocked carboxyl function (B). Incubation of this product B with carboxypeptidase A liberated only the C-terminal alanine of the B-chain, but not the asparagine of the C-terminus of the A-chain. Chymotryptic digestion of the isolated S-sulfonate A-chain derivative (C) followed by high-voltage electrophoresis confirmed that the carboxyl function of asparagine A21 was blocked. In order to determine the free carboxyl functions of the A-chain derivative C, it was coupled with glycine methyl ester yielding D. Amino acid analysis of the chymotryptic peptides of D showed that the carboxyl functions of glutamic acid A4 and A17 had been free prior to coupling. The amino acid analysis of the enzymatic hydrolysate (subtilisin, aminopeptidase M) of the A-chain derivative C showed an additional peak with an elution position identical to the model compound aminosuccinimide. The biological activity of the [Asm A21[insulin was found to be about 40% in the fat cell test and 13.2 units/mg measured by the mouse convulsion method.

  15. N=2 AdS supergravity and supercurrents

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We consider the minimal off-shell formulation for four-dimensional N=2 supergravity with a cosmological term, in which the second compensator is an improved tensor multiplet. We use it to derive a linearized supergravity action (and its dual versions) around the anti-de Sitter (AdS) background in terms of three N=2 off-shell multiplets: an unconstrained scalar superfield, vector and tensor multiplets. This allows us to deduce the structure of the supercurrent multiplet associated with those supersymmetric theories which naturally couple to the supergravity formulation chosen, with or without a cosmological term. Finally, our linearized N=2 AdS supergravity action is reduced to N=1 superspace. The result is a sum of two N=1 linearized actions describing (i) old minimal supergravity; and (ii) an off-shell massless gravitino multiplet. We also derive dual formulations for the massless N=1 gravitino multiplet in AdS. As a by-product of our consideration, we derive the consistent supergravity extension of the N=1 ...

  16. 21 CFR 522.1160 - Insulin.

    Science.gov (United States)

    2010-04-01

    ...) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units (IU) of insulin. (2) Each mL of protamine zinc recombinant human insulin suspension contains 40 IU of... clinical signs in dogs with diabetes mellitus. (iii) Limitations. Federal law restricts this drug to use...

  17. Insulin receptor knock-out mice.

    Science.gov (United States)

    Accili, D

    1997-04-01

    Targeted mutagenesis of the insulin receptor gene in mice has yielded unexpected results. This article reviews recent findings and analyzes this animal model can further our understanding of the mechanism of insulin action and its impairment in non-insulin-dependent diabetes mellitus is analyzed. (Trends Endocrinol Metab 1997;8:101-104). Published 1997 by Elsevier Science Inc.

  18. Lysosomal proteolysis: effects of aging and insulin.

    Science.gov (United States)

    Gromakova, I A; Konovalenko, O A

    2003-07-01

    Age-related characteristics of the effect of insulin on the activity of lysosomal proteolytic enzymes were studied. The relationship between the insulin effect on protein degradation and insulin degradation was analyzed. The effect of insulin on the activities of lysosomal enzymes was opposite in young and old rats (inhibitory in 3-month-old and stimulatory in 24-month-old animals). The activities of proteolytic enzymes were regulated by insulin in a glucose-independent manner: similar hypoglycemic effects of insulin in animals of different ages were accompanied by opposite changes in the activities of lysosomal enzymes. The inhibition of lysosomal enzymes by insulin in 3-month-old rats is consistent with a notion on the inhibitory effect of insulin on protein degradation. An opposite insulin effect in 24-month-old rats (i.e., stimulation of proteolytic activity by insulin) may be partly associated with attenuation of the degradation of insulin, resulting in disturbances in signaling that mediates the regulatory effects of insulin on protein degradation.

  19. Insulin: pancreatic secretion and adipocyte regulation.

    Science.gov (United States)

    Baumgard, L H; Hausman, G J; Sanz Fernandez, M V

    2016-01-01

    Insulin is the primary acute anabolic coordinator of nutrient partitioning. Hyperglycemia is the main stimulant of insulin secretion, but other nutrients such as specific amino acids, fatty acids, and ketoacids can potentiate pancreatic insulin release. Incretins are intestinal hormones with insulinotropic activity and are secreted in response to food ingestion, thus integrating diet chemical composition with the regulation of insulin release. In addition, prolactin is required for proper islet development, and it stimulates β-cell proliferation. Counterintuitively, bacterial components appear to signal insulin secretion. In vivo lipopolysaccharide infusion acutely increases circulating insulin, which is paradoxical as endotoxemia is a potent catabolic condition. Insulin is a potent anabolic orchestrator of nutrient partitioning, and this is particularly true in adipocytes. Insulin dictates lipid accretion in a dose-dependent manner during preadipocyte development in adipose tissue-derived stromal vascular cell culture. However, in vivo studies focused on insulin's role in regulating adipose tissue metabolism from growing, and market weight pigs are sometimes inconsistent, and this variability appears to be animal, age and depot dependent. Additionally, porcine adipose tissue synthesizes and secretes a number of adipokines (leptin, adiponectin, and so forth) that directly or indirectly influence insulin action. Therefore, because insulin has an enormous impact on agriculturally important phenotypes, it is critical to have a better understanding of how insulin homeostasis is governed.

  20. Insulin sensitivity : modulation by the brain

    NARCIS (Netherlands)

    Coomans, Claudia Pascalle

    2012-01-01

    The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated gluc

  1. Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA, total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL and fatty (ZF rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA. We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

  2. Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis

    OpenAIRE

    Alvarez, Jessica A.; Ambika Ashraf

    2010-01-01

    Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity. This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity. Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with insulin resistance, although direct measurements of insulin sensitivity are required for confirmation. Report...

  3. Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.

    OpenAIRE

    1991-01-01

    Diabetes mellitus is characterized by insulin deficiency and high plasma glucagon levels, which can be normalized by insulin replacement. It has previously been reported that glucagon gene expression is negatively regulated by insulin at the transcriptional level. By transfection studies, I have now localized a DNA control element that mediates insulin effects on glucagon gene transcription. This element also confers insulin responsiveness to a heterologous promoter. DNA-binding proteins that...

  4. Insulin resistance and cardiovascular disease.

    Science.gov (United States)

    Egan, B M; Greene, E L; Goodfriend, T L

    2001-06-01

    Cardiovascular risk factors cluster in obese individuals. Insulin resistance emerges as a common pathogenetic denominator underlying the risk factor cluster. Defects in nonesterified fatty acids metabolism have been implicated in the abnormal lipid and glucose metabolism which characterize the cluster. Other evidence also leads to the adipocyte as an important contributor to the risk factor cluster and cardiovascular complications through effects not only on fatty acids but also on leptin, plasminogen activator inhibitor-1, and angiotensinogen, to name a few. Fatty acids are elevated among abdominally obese individuals, are more resistant to suppression by insulin, and may contribute to hypertension. Fatty acids may affect blood pressure by inhibiting endothelial nitric oxide synthase activity and impairing endothelium-dependent vasodilation. Fatty acids increase alpha1-adrenoceptor-mediated vascular reactivity and enhance the proliferation and migration of cultured vascular smooth-muscle cells. Several effects of fatty acids are mediated through oxidative stress. Fatty acids can also interact with other facets of cluster, including increased angiotensin II, to accentuate oxidative stress. Oxidative stress, in turn, is implicated in the pathogenesis of insulin resistance, hypertension, vascular remodeling, and vascular complications. A clearer delineation of the key reactive oxygen signaling pathways and the impact of various interventions on these pathways could facilitate a rationale approach to antioxidant therapy and improved outcomes among the rapidly growing number of high-risk, insulin-resistant, obese individuals.

  5. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  6. Obesity genes and insulin resistance

    Science.gov (United States)

    Belkina, Anna C.; Denis, Gerald V.

    2011-01-01

    Purpose of review The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of ‘metabolically healthy but obese’ (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. Recent findings The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Summary Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID:20585247

  7. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophy

  8. Continue subcutane insuline-infusie

    OpenAIRE

    Ballegooie, Evert van

    1984-01-01

    In dit proefschrift worden de resultaten beschreven van een onderzoek naar: (1) de rol van bloedsuikerstrips en insuline-infusiepompjes bij de behandeling van diabetes mellitus; (2) de invloed van een verbetering van de diabetesregulatie op het verloop van de nefro-, neuro- en retinopathie en (3) de uitkomst van de zwangerschap bij diabetische gravidae na behandeling met een infusiepompje. ... Zie: Samenvatting

  9. Continue subcutane insuline-infusie

    NARCIS (Netherlands)

    Ballegooie, Evert van

    1984-01-01

    In dit proefschrift worden de resultaten beschreven van een onderzoek naar: (1) de rol van bloedsuikerstrips en insuline-infusiepompjes bij de behandeling van diabetes mellitus; (2) de invloed van een verbetering van de diabetesregulatie op het verloop van de nefro-, neuro- en retinopathie en (3) de

  10. 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.

  11. Intellectual mobile Ad Hoc networks

    OpenAIRE

    Sova, Oleg; Romanjuk, Valeriy; Bunin, Sergey; Zhuk, Pavlo

    2012-01-01

    In this article intellectualization of Mobile Ad Hoc Networks resources management is offered. It was proposed decomposition of the primary goal of MANET functioning into easy subgoals, and fragment of the MANET node target structure is presented.

  12. Combining GLP-1 receptor agonists with insulin

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Vilsbøll, T

    2013-01-01

    physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose...... potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose. In this review, the physiological and pharmacological rationale...

  13. Supergravity one-loop corrections on AdS7 and AdS3, higher spins and AdS/CFT

    Directory of Open Access Journals (Sweden)

    Matteo Beccaria

    2015-03-01

    Full Text Available As was shown earlier, the one-loop correction in 10d supergravity on AdS5×S5 corresponds to the contributions to the vacuum energy and 4d boundary conformal anomaly which are minus the values for one N=4 Maxwell supermultiplet, thus reproducing the subleading term in the N2−1 coefficient in the dual SU(N SYM theory. We perform similar one-loop computations in 11d supergravity on AdS7×S4 and 10d supergravity on AdS3×S3×T4. In the AdS7 case we find that the corrections to the 6d conformal anomaly a-coefficient and the vacuum energy are again minus the ones for one (2,0 tensor multiplet, suggesting that the total a-anomaly coefficient for the dual (2,0 theory is 4N3−9/4N−7/4 and thus vanishes for N=1. In the AdS3 case the one-loop correction to the vacuum energy or 2d central charge turns out to be equal to that of one free (4,4 scalar multiplet, i.e. is c=+6. This reproduces the subleading term in the central charge c=6(Q1Q5+1 of the dual 2d CFT describing decoupling limit of D5–D1 system. We also present the expressions for the 6d a-anomaly coefficient and vacuum energy contributions of general-symmetry higher spin field in AdS7 and consider their application to tests of vectorial AdS/CFT with the boundary conformal 6d theory represented by free scalars, spinors or rank-2 antisymmetric tensors.

  14. 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;

    2005-01-01

    In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....

  15. Entanglement Temperature and Perturbed AdS$_3$ Geometry

    CERN Document Server

    Levine, Gregory

    2015-01-01

    In analogy to the first law of thermodynamics, the increase in entanglement entropy $\\delta S$ of a conformal field theory (CFT) is proportional to the increase in energy, $\\delta E$, of the subsystem divided by an effective entanglement temperature, $T_E$. Extending this analogy, we study entanglement entropy when the subsystem is perturbed by applying an external field, expressed as a coupling to a local marginal operator in the CFT. We show that the resulting entropy change is associated with a change in the entanglement temperature itself, leading to an equation analogous to the Clausius relation. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature, $\\delta T_E(x)$ of the CFT and the perturbation of the bulk AdS metric. Using the AdS$_3$ minimal surface as a probe, we can construct bulk metric perturbations from an exact numerical computation of the entanglement temperature in a two dimensional $c=1$ boundary theory deformed by a marginal perturbati...

  16. Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players.

    Science.gov (United States)

    Gąsiorowski, Kazimierz; Brokos, Barbara; Leszek, Jerzy; Tarasov, V V; Ashraf, Ghulam Md; Aliev, Gjumrakch

    2017-01-03

    Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g.: ceramide, products of advanced glycation) and ROS-modified cellular components, together with activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy.

  17. Crosstalk between growth hormone and insulin signaling.

    Science.gov (United States)

    Xu, Jie; Messina, Joseph L

    2009-01-01

    Growth Hormone (GH) is a major growth-promoting and metabolic regulatory hormone. Interaction of GH with its cell surface GH receptor (GHR) causes activation of the GHR-associated cytoplasmic tyrosine kinase, JAK2, and activation of several signaling pathways, including the STATs, ERK1/2, and PI3K pathways. Insulin is also a key hormone regulating metabolism and growth. Insulin binding to the insulin receptor (IR) results in phosphorylation/activation of the IR, and activates the PI3K/Akt and ERK1/2 pathways. Due to their important roles in growth and metabolism, GH and insulin can functionally interact with each other, regulating cellular metabolism. In addition, recent data suggests that GH and insulin can directly interact by signaling crosstalk. Insulin regulation of GH signaling depends on the duration of exposure to insulin. Transient insulin exposure enhances GH-induced activation of MEK/ERK pathway through post-GHR mechanisms, whereas prolonged insulin exposure inhibits GH-induced signaling at both receptor and postreceptor levels. Chronic excessive GH interferes with insulin's activation of the IR/IRS/PI3K pathway and several proteins are involved in the mechanisms underlying GH-induced insulin resistance.

  18. Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose-Dependent Hepatic Insulin Production.

    Directory of Open Access Journals (Sweden)

    Tausif Alam

    Full Text Available Type 1 diabetes mellitus (T1DM is caused by immune destruction of insulin-producing pancreatic β-cells. Commonly used insulin injection therapy does not provide a dynamic blood glucose control to prevent long-term systemic T1DM-associated damages. Donor shortage and the limited long-term success of islet transplants have stimulated the development of novel therapies for T1DM. Gene therapy-based glucose-regulated hepatic insulin production is a promising strategy to treat T1DM. We have developed gene constructs which cause glucose-concentration-dependent human insulin production in liver cells. A novel set of human insulin expression constructs containing a combination of elements to improve gene transcription, mRNA processing, and translation efficiency were generated as minicircle DNA preparations that lack bacterial and viral DNA. Hepatocytes transduced with the new constructs, ex vivo, produced large amounts of glucose-inducible human insulin. In vivo, insulin minicircle DNA (TA1m treated streptozotocin (STZ-diabetic rats demonstrated euglycemia when fasted or fed, ad libitum. Weight loss due to uncontrolled hyperglycemia was reversed in insulin gene treated diabetic rats to normal rate of weight gain, lasting ∼1 month. Intraperitoneal glucose tolerance test (IPGT demonstrated in vivo glucose-responsive changes in insulin levels to correct hyperglycemia within 45 minutes. A single TA1m treatment raised serum albumin levels in diabetic rats to normal and significantly reduced hypertriglyceridemia and hypercholesterolemia. Elevated serum levels of aspartate transaminase, alanine aminotransferase, and alkaline phosphatase were restored to normal or greatly reduced in treated rats, indicating normalization of liver function. Non-viral insulin minicircle DNA-based TA1m mediated glucose-dependent insulin production in liver may represent a safe and promising approach to treat T1DM.

  19. [Insulin-induced lipohypertrophy treated by liposuction].

    Science.gov (United States)

    Brun, A; Comparin, J-P; Voulliaume, D; Chekaroua, K; Foyatier, J-L; Perrot, P

    2007-06-01

    The incidence of insulin-dependent diabetes mellitus increase permanently, with early diagnosis. Insulin is the treatment of this pathology. Insulin therapy is associated with complication such as lipodystrophies at injection sites leading functional and aesthetics disorders (pain, reduction of treatment efficiency, haematomas and oedemas). Our report two cases to illustrate the effectiveness of the suction-assisted lipectomy (SAL) on these lipodystrophies. We present two cases of insulin dependent diabetics patients with lipodystrophies of thighs, abdomen, and shoulders treated by SAL. The various analyzed parameters are: aesthetic aspect, efficiency of insulin treatment, ease injection, and pain reduction. We observe a significant reduction of insulin dose necessary to obtain a normoglycemia half time. This treatment allow a better control of pain, control of haematomas and oedemas at the injection sites and an aesthetic improvement. The lipoaspiration is thus a simple and effective treatment of lipodystrophies due to insulin.

  20. Insulin-responsiveness of tumor growth.

    Science.gov (United States)

    Chantelau, Ernst

    2009-05-01

    In October 2008, the 2nd International Insulin & Cancer Workshop convened roughly 30 researchers from eight countries in Düsseldorf/Germany. At this meeting, which was industry-independent like the preceding one in 2007, the following issues were discussed a) association between certain cancers and endogenous insulin production in humans, b) growth-promoting effects of insulin in animal experiments, c) mitogenic and anti-apoptotic activity of pharmaceutic insulin and insulin analogues in in vitro experiments, d) potential mechanisms of insulin action on cell growth, mediated by IGF-1 receptor and insulin receptor signaling, and e) IGF-1 receptor targeting for inhibition of tumor growth. It was concluded that further research is necessary to elucidate the clinical effects of these observations, and their potential for human neoplastic disease and treatment.

  1. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  2. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of Pioglitazone, Metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study

    Directory of Open Access Journals (Sweden)

    Kleine Iris

    2011-07-01

    Full Text Available Abstract Background We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. Methods In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA1C 6.5% - 8.5%, age 30 - 75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A bid 850 mg metformin (n = 42, (B bid 15 mg pioglitazone (n = 40, or (C 30 mg pioglitazone plus 1.7 g metformin (n = 39 over 6 months. Matrix Metal Proteinase 9 (MMP-9 was primary objective, together with biomarkers of CV risk. Results Pioglitazone (B reduced MMP-9 versus baseline by 54.1 + 187.1 ng/mL, with metformin (A it was increased by 49.6 + 336.2 ng/mL (p = 0.0345; B vs. A, and with the combination of both (C it was decreased by 67.8 + 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695. After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043 and for A vs. C (p = 0.0289. Insulin dosage was reduced by 7.3 units in group B (p 1C was only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C. Conclusions Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.

  3. Chromium-Insulin Reduces Insulin Clearance and Enhances Insulin Signaling by Suppressing Hepatic Insulin-Degrading Enzyme and Proteasome Protein Expression in KKAy Mice.

    Science.gov (United States)

    Wang, Zhong Q; Yu, Yongmei; Zhang, Xian H; Komorowski, James

    2014-01-01

    JDS-chromium-insulin (CRI)-003 is a novel form of insulin that has been directly conjugated with chromium (Cr) instead of zinc. Our hypothesis was that CRI enhances insulin's effects by altering insulin-degrading enzyme (IDE) and proteasome enzymes. To test this hypothesis, we measured hepatic IDE content and proteasome parameters in a diabetic animal model. Male KKAy mice were randomly divided into three groups (n = 8/group); Sham (saline), human regular insulin (Reg-In), and chromium conjugated human insulin (CRI), respectively. Interventions were initiated at doses of 2 U insulin/kg body weight daily for 8-weeks. Plasma glucose and insulin were measured. Hepatic IDE, proteasome, and insulin signaling proteins were determined by western blotting. Insulin tolerance tests at week 7 showed that both insulin treatments significantly reduced glucose concentrations and increased insulin levels compared with the Sham group, CRI significantly reduced glucose at 4 and 6 h relative to Reg-In (P < 0.05), suggesting the effects of CRI on reducing glucose last longer than Reg-In. CRI treatment significantly increased hepatic IRS-1 and Akt1 and reduced IDE, 20S as well as 19S protein abundance (P < 0.01, P < 0.05, and P < 0.001, respectively), but Reg-In only significantly increased Akt1 (P < 0.05). Similar results were also observed in Reg-In- and CRI-treated HepG2 cells. This study, for the first time, demonstrates that CRI reduces plasma insulin clearance by inhibition of hepatic IDE protein expression and enhances insulin signaling as well as prevents degradation of IRS-1 and IRS-2 by suppressing ubiquitin-proteasome pathway in diabetic mice.

  4. AdS Chern-Simons Gravity induces Conformal Gravity

    CERN Document Server

    Aros, Rodrigo

    2013-01-01

    The leitmotif of this paper is the question of whether four- and higher even-dimensional Conformal Gravities do have a Chern-Simons pedigree. We show that Weyl gravity can be obtained as dimensional reduction of a five-dimensional Chern-Simons action for a suitable (gauged-fixed, tractor-like) five-dimensional AdS connection. The gauge-fixing and dimensional reduction program admits a readily generalization to higher dimensions for the case of certain conformal gravities obtained by contractions of the Weyl tensor.

  5. Reentrant Phase Transitions in Rotating AdS Black Holes

    CERN Document Server

    Altamirano, Natacha; Mann, Robert B

    2013-01-01

    We study the thermodynamics of higher-dimensional singly spinning asymptotically AdS black holes in the canonical (fixed J) ensemble of extended phase space, where the cosmological constant is treated as pressure and the corresponding conjugate quantity is interpreted as thermodynamic volume. Along with the usual small/large black hole phase transition, we find a new phenomenon of reentrant phase transitions for all d>5 dimensions, in which a monotonic variation of the temperature yields two phase transitions from large to small and back to large black holes. This situation is similar to that seen in multicomponent liquids.

  6. Internal Structure of Charged AdS Black Holes

    CERN Document Server

    Bhattacharjee, Srijit; Virmani, Amitabh

    2016-01-01

    When an electrically charged black hole is perturbed its inner horizon becomes a singularity, often referred to as the Poisson-Israel mass inflation singularity. Ori constructed a model of this phenomenon for asymptotically flat black holes, in which the metric can be determined explicitly in the mass inflation region. In this paper we implement the Ori model for charged AdS black holes. We find that the mass function inflates faster than the flat space case as the inner horizon is approached. Nevertheless, the mass inflation singularity is still a weak singularity: although spacetime curvature becomes infinite, tidal distortions remain finite on physical objects attempting to cross it.

  7. Duality invariance of s≥32 fermions in AdS

    Directory of Open Access Journals (Sweden)

    S. Deser

    2014-11-01

    Full Text Available We show that in D=4 AdS, s≥3/2 partially massless (PM fermions retain the duality invariances of their flat space massless counterparts. They have tuned ratios m2/M2≠0 that turn them into sums of effectively massless unconstrained helicity ±(s,⋯,32 excitations, shorn of the lowest (non-dual helicity ±12-rung and — more generally — of succeeding higher rung as well. Each helicity mode is separately duality invariant, like its flat space counterpart.

  8. M-Theory solutions with AdS factors

    CERN Document Server

    Gauntlett, J P; Pakis, S; Waldram, D; Gauntlett, Jerome P.; Kim, Nakwoo; Pakis, Stathis; Waldram, Daniel

    2002-01-01

    Solutions of D=7 maximal gauged supergravity are constructed with metrics that are a product of a n-dimensional anti-de Sitter (AdS) space, with n=2,3,4,5, and certain Einstein manifolds. The gauge fields have the same form as in the recently constructed solutions describing the near-horizon limits of M5-branes wrapping supersymmetric cycles. The new solutions do not preserve any supersymmetry and can be uplifted to obtain new solutions of D=11 supergravity, which are warped and twisted products of the D=7 metric with a squashed four-sphere. Some aspects of the stability of the solutions are discussed.

  9. M-theory solutions with AdS factors

    Energy Technology Data Exchange (ETDEWEB)

    Gauntlett, Jerome P [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Kim, Nakwoo [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Pakis, Stathis [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Waldram, Daniel [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)

    2002-08-07

    Solutions of D=7 maximal gauged supergravity are constructed with metrics that are a product of an n-dimensional anti-de Sitter (AdS) space, with n=2, 3, 4, 5, and certain Einstein manifolds. The gauge fields have the same form as in the recently constructed solutions describing the near-horizon limits of M5-branes wrapping supersymmetric cycles. The new solutions do not preserve any supersymmetry and can be uplifted to obtain new solutions of D=11 supergravity, which are warped and twisted products of the D=7 metric with a squashed four-sphere. Some aspects of the stability of the solutions are discussed.

  10. Most general AdS_3 boundary conditions

    CERN Document Server

    Grumiller, Daniel

    2016-01-01

    We consider the most general asymptotically anti-de Sitter boundary conditions in three-dimensional Einstein gravity with negative cosmological constant. The metric contains in total twelve independent functions, six of which are interpreted as chemical potentials (or non-normalizable fluctuations) and the other half as canonical boundary charges (or normalizable fluctuations). Their presence modifies the usual Fefferman-Graham expansion. The asymptotic symmetry algebra consists of two sl(2)_k current algebras, the levels of which are given by k=l/(4G_N), where l is the AdS radius and G_N the three-dimensional Newton constant.

  11. Coherent Cascade: Collapsing Solutions in Global AdS

    CERN Document Server

    Freivogel, Ben

    2015-01-01

    We analyze the gravitational dynamics of a classical scalar field that sometimes leads to blackhole formation in asymptotically AdS spacetime at the shortest nonlinear time scale. We present strong evidence that the dynamics is governed by a "coherent cascade", with all modes remaining in phase as the energy flows to higher frequencies into a power-law spectrum. Using a coherent phase ansatz, we analytically find these power-law solutions. We show how the particular power is determined by the scaling properties of the interaction coefficients. Our result agrees with existing numerical results in 4+1 dimensions, and makes predictions in higher dimensions.

  12. Heavy quark potential from deformed AdS5 models

    Science.gov (United States)

    Zhang, Zi-qiang; Hou, De-fu; Chen, Gang

    2017-04-01

    In this paper, we investigate the heavy quark potential in some holographic QCD models. The calculation relies on a modified renormalization scheme mentioned in a previous work of Albacete et al. After studying the heavy quark potential in Pirner-Galow model and Andreev-Zakharov model, we extend the discussion to a general deformed AdS5 case. It is shown that the obtained potential is negative definite for all quark-antiquark separations, differs from that using the usual renormalization scheme.

  13. Inhibition of insulin amyloid fibril formation by cyclodextrins.

    Science.gov (United States)

    Kitagawa, Keisuke; Misumi, Yohei; Ueda, Mitsuharu; Hayashi, Yuya; Tasaki, Masayoshi; Obayashi, Konen; Yamashita, Taro; Jono, Hirofumi; Arima, Hidetoshi; Ando, Yukio

    2015-01-01

    Localized insulin-derived amyloid masses occasionally form at the site of repeated insulin injections in patients with insulin-dependent diabetes and cause subcutaneous insulin resistance. Various kinds of insulin including porcine insulin, human insulin, and insulin analogues reportedly formed amyloid fibrils in vitro and in vivo, but the impact of the amino acid replacement in insulin molecules on amyloidogenicity is largely unknown. In the present study, we demonstrated the difference in amyloid fibril formation kinetics of human insulin and insulin analogues, which suggests an important role of the C-terminal domain of the insulin B chain in nuclear formation of amyloid fibrils. Furthermore, we determined that cyclodextrins, which are widely used as drug carriers in the pharmaceutical field, had an inhibitory effect on the nuclear formation of insulin amyloid fibrils. These findings have significant implications for the mechanism underlying insulin amyloid fibril formation and for developing optimal additives to prevent this subcutaneous adverse effect.

  14. Effect of insulin and glucose on the activity of insulin-degrading enzymes in rat liver.

    Science.gov (United States)

    Jurcovicová, J; Németh, S; Vigas, M

    1977-09-01

    The degradation of insulin by insulin protease and glutathion-insulin transhydrogenase (glutathioneproteindisulphide oxidoreductase--EC 1.8.4.2, GIT) was measured in rat liver either after replacing food and water by 15% glucose solution, or after daily insulin administration 8 U daily for 3 days or after fasting. The breakdown of radioiodinated insulin was followed by measuring the increase of TCA soluble radioactivity during incubation of cell fractions with 125I insulin at 37 degrees C. The highest GIT activity was observed in liver microsomes of rats after glucose feeding and after insulin administration, whereas enzyme activity of fasted animals did not essentially differ from corresponding values of normally fed controls. The insulin protease in cytosol of liver cells remained unchanged after these procedures. The important role of GIT in insulin degradation seems to be conclusively demonstrated.

  15. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.;

    2012-01-01

    and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...... to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining......An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...

  16. B22 Glu Des-B30 Insulin: A Novel Monomeric Insulin

    Institute of Scientific and Technical Information of China (English)

    Hai-Juan DU; Jia-Hao SHI; Da-Fu CUI; You-Shang ZHANG

    2006-01-01

    Studies on monomeric insulin with reduced self-association are important in the development of insulin pharmaceutical preparations with rapid hypoglycemic action on patients with diabetes. Here we report a novel monomeric insulin, B22 Glu des-B30 insulin, prepared from a single chain insulin precursor with B22 Arg mutated to Glu, which was expressed in Pichia pastoris and converted to B22 Glu des-B30 insulin by tryptic digestion. It still retains 50% of the in vivo biological activity of porcine insulin and does not form a dimer even at a concentration of 10 mg/ml, showing that B22 Glu plays a key role in reducing the selfassociation of the insulin molecule without greatly reducing its biological activity. This novel monomeric insulin might have potential applications in the clinic.

  17. Denosumab Inhibition of RANKL and Insulin Resistance in Postmenopausal Women with Osteoporosis.

    Science.gov (United States)

    Lasco, Antonino; Morabito, Nunziata; Basile, Giorgio; Atteritano, Marco; Gaudio, Agostino; Giorgianni, Grazia Maria; Morini, Elisabetta; Faraci, Bianca; Bellone, Federica; Catalano, Antonino

    2016-02-01

    The tumor necrosis factor-related cytokine receptor activator of nuclear factor kappa B ligand (RANKL) has been proposed as predictor of incident type 2 diabetes mellitus, and experimental blockade of RANKL resulted in a marked improvement of glucose tolerance. Denosumab is a fully human monoclonal antibody that binds to RANKL and prevents osteoclast formation, function and survival, leading to fracture risk reduction. The aim of our study was to investigate glucometabolic parameters, insulin resistance, and lipid profile in non-diabetic women receiving denosumab. Forty-eight women with postmenopausal osteoporosis were enrolled and treated with a subcutaneous dose (60 mg) of denosumab. At baseline and after 4, 12, ad 24 weeks, insulin resistance was computed by homeostasis model assessment of insulin resistance (HOMA-IR) and total cholesterol, triglycerides and HDL cholesterol were also measured. At baseline and after 24 weeks, bone turn-over markers were also evaluated. After denosumab administration, with the exception of a slight reduction of insulin and HOMA-IR values after 4 weeks (p insulin resistance were significantly changed. Lipid parameters remained unchanged at each time-points of this study. A reduction of C-telopeptide of type 1 collagen (-63%, p women, denosumab was not associated with relevant modification of insulin resistance and lipid profile.

  18. Introducing ADS 2.0

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Murray, S. S.

    2014-01-01

    In the spring of 1993, the Smithsonian/NASA Astrophysics Data System (ADS) first launched its bibliographic search system. It was known then as the ADS Abstract Service, a component of the larger Astrophysics Data System effort which had developed an interoperable data system now seen as a precursor of the Virtual Observatory. As a result of the massive technological and sociological changes in the field of scholarly communication, the ADS is now completing the most ambitious technological upgrade in its twenty-year history. Code-named ADS 2.0, the new system features: an IT platform built on web and digital library standards; a new, extensible, industrial strength search engine; a public API with various access control capabilities; a set of applications supporting search, export, visualization, analysis; a collaborative, open source development model; and enhanced indexing of content which includes the full-text of astronomy and physics publications. The changes in the ADS platform affect all aspects of the system and its operations, including: the process through which data and metadata are harvested, curated and indexed; the interface and paradigm used for searching the database; and the follow-up analysis capabilities available to the users. This poster describes the choices behind the technical overhaul of the system, the technology stack used, and the opportunities which the upgrade is providing us with, namely gains in productivity and enhancements in our system capabilities.

  19. Rindler-AdS/CFT

    CERN Document Server

    Parikh, Maulik

    2012-01-01

    In anti-de Sitter space a highly accelerating observer perceives a Rindler horizon. The two Rindler wedges in AdS_{d+1} are holographically dual to an entangled conformal field theory that lives on two boundaries with geometry R x H_{d-1}. For AdS_3, the holographic duality is especially tractable, allowing quantum-gravitational aspects of Rindler horizons to be probed. We recover the thermodynamics of Rindler-AdS space directly from the boundary conformal field theory. We derive the temperature from the two-point function and obtain the Rindler entropy density precisely, including numerical factors, using the Cardy formula. We also probe the causal structure of the spacetime, and find from the behavior of the one-point function that the CFT "knows" when a source has fallen across the Rindler horizon. This is so even though, from the bulk point of view, there are no local signifiers of the presence of the horizon. Finally, we discuss an alternate foliation of Rindler-AdS which is dual to a CFT living in de Si...

  20. Excess exposure to insulin is the primary cause of insulin resistance and its associated atherosclerosis.

    Science.gov (United States)

    Cao, Wenhong; Ning, Jie; Yang, Xuefeng; Liu, Zhenqi

    2011-11-01

    The main goal of this review is to provide more specific and effective targets for prevention and treatment of insulin resistance and associated atherosclerosis. Modern technologies and medicine have vastly improved human health and prolonged the average life span of humans primarily by eliminating various premature deaths and infectious diseases. The modern technologies have also provided us abundant food and convenient transportation tools such as cars. As a result, more people are becoming overfed and sedentary. People are generally ingesting more calories than their bodies' need, leading to the so-called "positive energy imbalance", which is inseparable from the development of insulin resistance and its associated atherosclerosis. A direct consequence of insulin resistance is hyperinsulinemia. The current general view is that insulin is not functional properly in the presence of insulin resistance. Thus, the role of insulin itself in the development of insulin resistance and associated atherosclerosis has not been recognized. We have recently observed that the basal level of insulin signaling is increased in the presence of insulin resistance and hyperinsulinemia. In this review, we will explain how the increased basal insulin signaling contributes to the development of insulin resistance and associated atherosclerosis. We will first explain how insulin causes insulin resistance through two arbitrary stages (before and after the presence of obvious insulin resistance), and, then, explain how the excess exposure to insulin and the relative insulin insufficiency contributes to the atherosclerotic diseases. We propose that blockade of the excess insulin signaling is a viable approach to prevent and/or reverse insulin resistance and its associated atherosclerosis.

  1. AdS twistors for higher spin theory

    CERN Document Server

    Cederwall, M

    2004-01-01

    We construct spectra of supersymmetric higher spin theories in D=4, 5 and 7 from twistors describing massless (super-)particles on AdS spaces. A massless twistor transform is derived in a geometric way from classical kinematics. Relaxing the spin-shell constraints on twistor space gives an infinite tower of massless states of a ``higher spin particle'', generalising previous work of Bandos et al. This can generically be done in a number of ways, each defining the states of a distinct higher spin theory, and the method provides a systematic way of finding these. We reproduce known results in D=4, minimal supersymmetric 5- and 7-dimensional models, as well as supersymmetrisations of Vasiliev's Sp-models as special cases. In the latter models a dimensional enhancement takes place, meaning that the theory lives on a space of higher dimension than the original AdS space, and becomes a theory of doubletons. This talk was presented at the XIXth Max Born Symposium ``Fundamental Interactions and Twistor-Like Methods''...

  2. AdCell: Ad Allocation in Cellular Networks

    CERN Document Server

    Alaei, Saeed; Liaghat, Vahid; Pei, Dan; Saha, Barna

    2011-01-01

    With more than four billion usage of cellular phones worldwide, mobile advertising has become an attractive alternative to online advertisements. In this paper, we propose a new targeted advertising policy for Wireless Service Providers (WSPs) via SMS or MMS- namely {\\em AdCell}. In our model, a WSP charges the advertisers for showing their ads. Each advertiser has a valuation for specific types of customers in various times and locations and has a limit on the maximum available budget. Each query is in the form of time and location and is associated with one individual customer. In order to achieve a non-intrusive delivery, only a limited number of ads can be sent to each customer. Recently, new services have been introduced that offer location-based advertising over cellular network that fit in our model (e.g., ShopAlerts by AT&T) . We consider both online and offline version of the AdCell problem and develop approximation algorithms with constant competitive ratio. For the online version, we assume tha...

  3. Quantum cat map dynamics on AdS$_2$

    CERN Document Server

    Axenides, Minos; Nicolis, Stam

    2016-01-01

    We present a toy model for the chaotic unitary scattering of single particle wave packets on the radial AdS$_2$ geometry of extremal BH horizons. Based on our recent work for the discretization of the AdS$_2$ space-time, which describes a finite and random geometry, by modular arithmetic, we investigate the validity of the eigenstate thermalization hypothesis (ETH), as well as that of the fast scrambling time bound conjecture (STB), for an observer with time evolution operator the quantum Arnol'd cat map (QACM). We find that the QACM, while possessing a linear spectrum, has eigenstates, which can be expressed in closed form, are found to be random and to satisfy the assumptions of the ETH.The implications are that the dynamics is described by a chaotic, unitary, single particle S-matrix, which completely delocalizes and randomizes initial gaussian wave packets . Applying results obtained by Dyson and Falk for the periods of the Arnol'd Cat Map(ACM),which are related to its mixing time, we also find that the t...

  4. A special road to AdS vacua

    CERN Document Server

    Cassani, Davide; Marrani, Alessio; Morales, Jose F; Samtleben, Henning

    2010-01-01

    We apply the techniques of special Kaehler geometry to investigate AdS_4 vacua of general N=2 gauged supergravities underlying flux compactifications of type II theories. We formulate the scalar potential and its extremization conditions in terms of a triplet of prepotentials P_x and their special Kaehler covariant derivatives only, in a form that recalls the potential and the attractor equations of N=2 black holes. We propose a system of first order equations for the P_x which generalize the supersymmetry conditions and yield non-supersymmetric vacua. Special geometry allows us to recast these equations in algebraic form, and we find an infinite class of new N=0 and N=1 AdS_4 solutions, displaying a rich pattern of non-trivial charges associated with NSNS and RR fluxes. Finally, by explicit evaluation of the entropy function on the solutions, we derive a U-duality invariant expression for the cosmological constant and the central charges of the dual CFT's.

  5. The CFT dual of AdS gravity with torsion

    CERN Document Server

    Klemm, Dietmar

    2007-01-01

    We consider the Mielke-Baekler model of three-dimensional AdS gravity with torsion, which has gravitational and translational Chern-Simons terms in addition to the usual Einstein-Hilbert action with cosmological constant. It is shown that the topological nature of the model leads to a finite Fefferman-Graham expansion. We derive the holographic stress tensor and the associated Ward identities and show that, due to the asymmetry of the left- and right-moving central charges, a Lorentz anomaly appears in the dual conformal field theory. Both the consistent and the covariant Weyl and Lorentz anomaly are determined, and the Wess-Zumino consistency conditions for the former are verified. Moreover we consider the most general solution with flat boundary geometry, which describes left-and right-moving gravitational waves on AdS_3 with torsion, and shew that in this case the holographic energy-momentum tensor is given by the wave profiles. The anomalous transformation laws of the wave profiles under diffeomorphisms p...

  6. AdS nonlinear instability: moving beyond spherical symmetry

    Science.gov (United States)

    Dias, Óscar J. C.; Santos, Jorge E.

    2016-12-01

    Anti-de Sitter (AdS) is conjectured to be nonlinear unstable to a weakly turbulent mechanism that develops a cascade towards high frequencies, leading to black hole formation (Dafermos and Holzegel 2006 Seminar at DAMTP (University of Cambridge) available at https://dpmms.cam.ac.uk/~md384/ADSinstability.pdf, Bizon and Rostworowski 2011 Phys. Rev. Lett. 107 031102). We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied by Bizon and Rostworowski. In contrast with Bizon and Rostworowski, we find that not all gravitational normal modes of AdS can be nonlinearly extended into periodic horizonless smooth solutions of the Einstein equation. In particular, we show that even seeds with a single normal mode can develop secular resonances, unlike the spherically symmetric scalar field collapse studied by Bizon and Rostworowski. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of Bizon and Rostworowski. We also show that weak turbulent perturbative theory predicts the existence of direct and inverse cascades, with the former dominating the latter for equal energy two-mode seeds.

  7. Smooth Causal Patches for AdS Black Holes

    CERN Document Server

    Raju, Suvrat

    2016-01-01

    We review the paradox of low energy excitations about an AdS black hole. An appropriately chosen unitary operator in the boundary theory can create a locally strong excitation near the black hole horizon, whose global energy is small as a result of the gravitational redshift. The paradox is that this seems to violate a general rule of statistical mechanics, which states that an operator with energy parametrically smaller than $k T$ cannot create a significant excitation in a thermal system. When we carefully examine the position dependence of the boundary unitary operator that produces the excitation and the bulk observable necessary to detect the anomalously large effect, we find that they do not both fit in a single causal patch. This follows from a remarkable property of position space AdS correlators that we establish explicitly, and resolves the paradox in a generic state of the system, since no combination of observers can both create the excitation and observe its effect. As a special case of our analy...

  8. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects coul

  9. Online Ad Slotting With Cancellations

    CERN Document Server

    Constantin, Florin; Muthukrishnan, S; Pal, Martin

    2008-01-01

    Many advertisers buy advertisements (ads) on the Internet or on traditional media and seek simple, online mechanisms to reserve ad slots in advance. Media publishers represent a vast and varying inventory, and they too seek automatic, online mechanisms for pricing and allocating such reservations. In this paper, we present and study a simple model for auctioning such ad slots in advance. Bidders arrive sequentially and report which slots they are interested in. The seller must decide immediately whether or not to grant a reservation. Our model allows a seller to accept reservations, but possibly cancel the allocations later and pay the bidder a cancellation compensation (bump payment). Our main result is an online mechanism to derive prices and bump payments that is efficient to implement. This mechanism has many desirable properties. It is individually rational; winners have an incentive to be honest and bidding one's true value dominates any lower bid. Our mechanism's efficiency is within a constant fractio...

  10. Three-chain insulin analogs demonstrate the importance of insulin secondary structure to bioactivity.

    Science.gov (United States)

    Wu, Fangzhou; Chabenne, Joseph R; Gelfanov, Vasily M; Mayer, John P; DiMarchi, Richard D

    2015-03-01

    This report describes the chemical synthesis and biological characterization of novel three-chain insulin analogs with a destabilized secondary structure. The analogs, obtained by chemical synthesis via a single-chain precursor and selective enzymatic digestion, were used to investigate the role of the highly conserved 'insulin fold'. Biological characterization through in vitro biochemical signaling showed extremely low activity at each insulin receptor when compared with native insulin. We conclude that the 'insulin fold' is a structural foundation that supports insulin biological action.

  11. Skeletal muscle and hepatic insulin signaling is maintained in heat-stressed lactating Holstein cows.

    Science.gov (United States)

    Xie, G; Cole, L C; Zhao, L D; Skrzypek, M V; Sanders, S R; Rhoads, M L; Baumgard, L H; Rhoads, R P

    2016-05-01

    Multiparous cows (n=12; parity=2; 136±8 d in milk, 560±32kg of body weight) housed in climate-controlled chambers were fed a total mixed ration (TMR) consisting primarily of alfalfa hay and steam-flaked corn. During the first experimental period (P1), all 12 cows were housed in thermoneutral conditions (18°C, 20% humidity) with ad libitum intake for 9 d. During the second experimental period (P2), half of the cows were fed for ad libitum intake and subjected to heat-stress conditions [WFHS, n=6; cyclical temperature 31.1 to 38.9°C, 20% humidity: minimum temperature humidity index (THI)=73, maximum THI=80.5], and half of the cows were pair-fed to match the intake of WFHS cows in thermal neutral conditions (TNPF, n=6) for 9 d. Rectal temperature and respiration rate were measured thrice daily at 0430, 1200, and 1630 h. To evaluate muscle and liver insulin responsiveness, biopsies were obtained immediately before and after an insulin tolerance test on the last day of each period. Insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT/protein kinase B (AKT), and phosphorylated AKT (p-AKT) were measured by Western blot analyses for both tissues. During P2, WFHS increased rectal temperature and respiration rate by 1.48°C and 2.4-fold, respectively. Heat stress reduced dry matter intake by 8kg/d and, by design, TNPF cows had similar intake reductions. Milk yield was decreased similarly (30%) in WFHS and TNPF cows, and both groups entered into a similar (-4.5 Mcal/d) calculated negative energy balance during P2. Insulin infusion caused a less rapid glucose disposal in P2 compared with P1, but glucose clearance did not differ between environments in P2. In liver, insulin increased p-AKT protein content in each period. Phosphorylation ratio of AKT increased 120% in each period after insulin infusion. In skeletal muscle, protein abundance of the IR, IRS, and AKT remained stable between periods and environment. Insulin increased skeletal muscle p-AKT in each

  12. Mechanisms underlying insulin deficiency-induced acceleration of β-amyloidosis in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Latha Devi

    Full Text Available Although evidence is accumulating that diabetes mellitus is an important risk factor for sporadic Alzheimer's disease (AD, the mechanisms by which defects in insulin signaling may lead to the acceleration of AD progression remain unclear. In this study, we applied streptozotocin (STZ to induce experimental diabetes in AD transgenic mice (5XFAD model and investigated how insulin deficiency affects the β-amyloidogenic processing of amyloid precursor protein (APP. Two and half months after 5XFAD mice were treated with STZ (90 mg/kg, i.p., once daily for two consecutive days, they showed significant reductions in brain insulin levels without changes in insulin receptor expression. Concentrations of cerebral amyloid-β peptides (Aβ40 and Aβ42 were significantly increased in STZ-treated 5XFAD mice as compared with vehicle-treated 5XFAD controls. Importantly, STZ-induced insulin deficiency upregulated levels of both β-site APP cleaving enzyme 1 (BACE1 and full-length APP in 5XFAD mouse brains, which was accompanied by dramatic elevations in the β-cleaved C-terminal fragment (C99. Interestingly, BACE1 mRNA levels were not affected, whereas phosphorylation of the translation initiation factor eIF2α, a mechanism proposed to mediate the post-transcriptional upregulation of BACE1, was significantly elevated in STZ-treated 5XFAD mice. Meanwhile, levels of GGA3, an adapter protein responsible for sorting BACE1 to lysosomal degradation, are indistinguishable between STZ- and vehicle-treated 5XFAD mice. Moreover, STZ treatments did not affect levels of Aβ-degrading enzymes such as neprilysin and insulin-degrading enzyme (IDE in 5XFAD brains. Taken together, our findings provide a mechanistic foundation for a link between diabetes and AD by demonstrating that insulin deficiency may change APP processing to favor β-amyloidogenesis via the translational upregulation of BACE1 in combination with elevations in its substrate, APP.

  13. The nursing observation of insulin aspart and insulin glargine in the treatment of pediatric type Ⅰ diabetes of children%门冬胰岛素联合甘精胰岛素治疗小儿1型糖尿病护理观察

    Institute of Scientific and Technical Information of China (English)

    丁波; 罗书立; 衣芳玲; 贾斐

    2014-01-01

    目的 探讨门冬胰岛素联合甘精胰岛素治疗小儿1型糖尿病的疗效及护理措施.方法 选取2011年10月~2013年10月我院收治的小儿1型糖尿病患儿69例,分为观察组(35例)和对照组(34例),对照组单纯给予门冬胰岛素治疗,观察组予门冬胰岛素联合甘精胰岛素治疗,并加强护理工作,比较两组患儿实验室检查指标以及低血糖发生率.结果 观察组空腹血糖(FBG)、餐后2h血糖(2 hBG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、胆固醇(TC)等实验室相关指标改善均优于对照组(P<0.05),且观察组低血糖发生率显著低于对照组(P<0.05),两组患儿的护理质量评分比较,差异有统计学意义(P<0.05).结论 门冬胰岛素联合甘精胰岛素治疗小儿1型糖尿病疗效确切,同时通过加强护理工作,能显著提高临床治疗效果,降低低血糖发生.

  14. Adding momentum to supersymmetric geometries

    Energy Technology Data Exchange (ETDEWEB)

    Lunin, Oleg, E-mail: olunin@albany.edu [Department of Physics, University at Albany (SUNY), Albany, NY 12222 (United States); Mathur, Samir D., E-mail: mathur.16@osu.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States); Turton, David, E-mail: turton.7@osu.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States)

    2013-03-11

    We consider general supersymmetric solutions to minimal supergravity in six dimensions, trivially lifted to IIB supergravity. To any such solution we add a traveling wave deformation involving the additional directions. The deformed solution is given in terms of a function which is harmonic in the background geometry. We also present a family of explicit examples describing microstates of the D1-D5 system on T{sup 4}. In the case where the background contains a large AdS region, the deformation is identified as corresponding to an action of a U(1) current of the D1-D5 orbifold CFT on a given state.

  15. Adding momentum to supersymmetric geometries

    CERN Document Server

    Lunin, Oleg; Turton, David

    2012-01-01

    We consider general supersymmetric solutions to minimal supergravity in six dimensions, trivially lifted to IIB supergravity. To any such solution we add a travelling-wave deformation involving the additional directions. The deformed solution is given in terms of a function which is harmonic in the background geometry. We also present a family of explicit examples describing microstates of the D1-D5 system on T^4. In the case where the background contains a large AdS region, the deformation is identified as corresponding to an action of a U(1) current of the D1-D5 orbifold CFT on a given state.

  16. CHEMICAL DERIVATION OF HUMAN INSULIN SUPERAGONISM

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The role of three highly conserved insulin residues TyrB26 was studied to better understand the relationship between insulin and receptor from rat adipose tissue plasma membranes. Insulin analogues with a single amino acid substitution or single N-methylation of the peptide bond in the position B26 were all shortened in the C-terminus of the B-chain by four amino acids. The effect of modifications was followed by the binding to the insulin receptor. From our results, we can deduce several conclusions: (1) the replacement of tyrosine in the position B26 by histidine, [N-MeHisB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide and [N-MeGluB26]-des-tetrapeptide- (B27~B30)-insulin-B26-amide, have no significant effect on the binding affinity and they show binding affinity 105%, 190% and 208%, respectively, of that of human insulin; (2) [AadB26] -des-tetrapeptide-(B27~B30)-insulin-B26-amide and [Phe(4-carboxyB26)]-des-tetrapeptide- (B27~B30)-insulin-B26-amide affect the potency highly positively in vitro studies; they show binding affinity 529 and 289 %, respectively, of that of human insulin.

  17. CHEMICAL DERIVATION OF HUMAN INSULIN SUPERAGONISM

    Institute of Scientific and Technical Information of China (English)

    MA Baoquan; KANG Wei; YAN Junkai

    2007-01-01

    The role of three highly conserved insulin residues TyrB26 was studied to better understand the relationship between insulin and receptor from rat adipose tissue plasma membranes. Insulin analogues with a single amino acid substitution or single N-methylation of the peptide bond in the position B26 were all shortened in the C-terminus of the B-chain by four amino acids. The effect of modifications was followed by the binding to the insulin receptor. From our results, we can deduce several conclusions: (1) the replacement of tyrosine in the position B26 by histidine,[N-MeHisB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide and [N-MeGluB26]-des-tetrapeptide(B27~B30)-insulin-B26-amide, have no significant effect on the binding affinity and they show binding affinity 105%, 190% and 208%, respectively, of that of human insulin; (2) [AadB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide and [Phe(4-carboxyB26)]-des-tetrapeptide(B27~B30)-insulin-B26-amide affect the potency highly positively in vitro studies; they show binding affinity 529 and 289 %, respectively, of that of human insulin.

  18. Obesity, inflammation, and insulin resistance

    OpenAIRE

    Luana Mota Martins; Ana Raquel Soares de Oliveira; Kyria Jayanne Clímaco Cruz; Francisco Leonardo Torres-Leal; Dilina do Nascimento Marreiro

    2014-01-01

    White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro- and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecu...

  19. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

    Science.gov (United States)

    Reiter, Chad E N; Wu, Xiaohua; Sandirasegarane, Lakshman; Nakamura, Makoto; Gilbert, Kirk A; Singh, Ravi S J; Fort, Patrice E; Antonetti, David A; Gardner, Thomas W

    2006-04-01

    Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

  20. Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

    Directory of Open Access Journals (Sweden)

    Chiou Shih-Hwa

    2010-07-01

    Full Text Available Abstract Background Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs offer renewable cells for generating insulin-producing cells (IPCs. Methods We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation. Results Here, we report adding extracellular matrix proteins (ECM such as fibronectin (FN or laminin (LAM enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor, PD98059 (MEK specific inhibitor or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM. Conclusions These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.

  1. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  2. Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Picone, Pasquale; Ditta, Lorena Anna; Sabatino, Maria Antonietta; Militello, Valeria; San Biagio, Pier Luigi; Di Giacinto, Maria Laura; Cristaldi, Laura; Nuzzo, Domenico; Dispenza, Clelia; Giacomazza, Daniela; Di Carlo, Marta

    2016-02-01

    A growing body of evidence shows the protective role of insulin in Alzheimer's disease (AD). A nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for Alzheimer's Disease (AD), is designed and synthetized. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation is chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility and hemocompatibility of the naked carrier is demonstrated. The insulin conjugated to the NG (NG-In) is protected by protease degradation and able to bind to insulin receptor (IR), as demonstrated by immunofluorescence measurements showing colocalization of NG-In(FITC) with IR. Moreover, after binding to the receptor, NG-In is able to trigger insulin signaling via AKT activation. Neuroprotection of NG-In against dysfunction induced by amyloid β (Aβ), a peptide mainly involved in AD, is verified. Finally, the potential of NG-In to be efficiently transported across the Blood Brain Barrier (BBB) is demonstrated. All together these results indicate that the synthesized NG-In is a suitable vehicle system for insulin deliver in biomedicine and a very promising tool to develop new therapies for neurodegenerative diseases.

  3. Holographic properties in three-dimensional AdS soliton using $AdS_3/CFT_2$

    CERN Document Server

    Peng, Yan

    2016-01-01

    We study the holographic description of a superconductor by the $AdS_{3}/CFT_{2}$ correspondence. The system is constructed with a Maxwell field and a charged scalar field coupled in the (2+1)-dimensional AdS soliton background. With analytical methods, we obtain the exact expression for the critical chemical potential as $\\mu_{c} = 1 + \\sqrt{1+m^2}$, which has also been generalized to higher dimensions as $\\mu_c \\thickapprox a + \\sqrt{m^2-m_{BF}^2}$ in this work. Around the phase transition points, we find a correspondence between the value of the scalar field at the tip and the scalar operator at infinity. We also arrive at the classical second order phase transition threshold exponent $\\beta=\\frac{1}{2}$ as the same as the mean field theory near the critical chemical potential. As the condensation becomes heavier, we show surprisingly that superconducting phases exist only in a certain range of the chemical potential, which is very different from higher-dimensional cases. And for the small enough negative ...

  4. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...

  5. Adherence to insulin treatment in insulin-naïve type 2 diabetic patients initiated on different insulin regimens

    Directory of Open Access Journals (Sweden)

    Gogas Yavuz D

    2015-08-01

    Full Text Available Dilek Gogas Yavuz, Sevim Ozcan, Oguzhan DeyneliDepartment of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, TurkeyObjective: We aimed to evaluate adherence to insulin treatment in terms of treatment persistence and daily adherence to insulin injections among insulin-naïve type 2 diabetic patients initiating insulin therapy with basal (long acting, basal-bolus, and premixed insulin regimens in a tertiary endocrinology outpatient clinic.Methods: A total of 433 (mean age of 55.5±13.0 years; 52.4% females insulin-naïve type 2 diabetic patients initiated on insulin therapy were included in this questionnaire-based phone interview survey at the sixth month of therapy. Via the telephone interview questions, patients were required to provide information about persistence to insulin treatment, self-reported blood glucose values, and side effects; data on demographics and diabetes characteristics were obtained from medical records.Results: Self-reported treatment withdrawal occurred in 20.1% patients, while 20.3% patients were nonadherent to daily insulin. Negative beliefs about insulin therapy (24.1% and forgetting injections (40.9% were the most common reasons for treatment withdrawal and dose skipping, respectively. Younger age (49.5±15.0 vs 56.4±12.0 years (P=0.001 and shorter duration of diabetes (4.8±4.3 vs 8.8±6.3 years (P=0.0008 and treatment duration (5.2±2.4 vs 10.7±2.4 months (P=0.0001 were noted, respectively, in discontinuers vs continuers. Basal bolus was the most commonly prescribed insulin regimen (51.0%, while associated with higher likelihood of skipping a dose than regular use (61.3% vs. 46.0%, P=0.04.Conclusions: Persistence to insulin therapy was poorer than anticipated but appeared to be higher in patients with the basal bolus regimen. Negative perceptions about insulin therapy seemed to be the main cause for poor adherence in our cohort.Keywords: type 2 diabetes, insulin treatment adherence

  6. Brownian motion in AdS/CFT

    NARCIS (Netherlands)

    de Boer, J.; Hubeny, V.E.; Rangamani, M.; Shigemori, M.

    2009-01-01

    We study Brownian motion and the associated Langevin equation in AdS/CFT. The Brownian particle is realized in the bulk spacetime as a probe fundamental string in an asymptotically AdS black hole background, stretching between the AdS boundary and the horizon. The modes on the string are excited by

  7. [Beyond immunopathogenesis. Insulin resistance and "epidermal dysfunction"].

    Science.gov (United States)

    Boehncke, W-H; Boehncke, S; Buerger, C

    2012-03-01

    Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize "epidermal dysfunction", thus complementing the immunomodulatory strategies of today's biologics.

  8. Animal models of insulin resistance: A review.

    Science.gov (United States)

    Sah, Sangeeta Pilkhwal; Singh, Barinder; Choudhary, Supriti; Kumar, Anil

    2016-12-01

    Insulin resistance can be seen as a molecular and genetic mystery, with a role in the pathophysiology of type 2 diabetes mellitus. It is a basis for a number of chronic diseases like hypertension, dyslipidemia, glucose intolerance, coronary heart disease, cerebral vascular disease along with T2DM, thus the key is to cure and prevent insulin resistance. Critical perspicacity into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by various transgenic and non-transgenic models which is not possible in human studies. The following review comprises the pathophysiology involved in insulin resistance, various factors causing insulin resistance, their screening and various genetic and non-genetic animal models highlighting the pathological and metabolic characteristics of each.

  9. Associations between depressive symptoms and insulin resistance

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Nijpels, G

    2006-01-01

    AIMS/HYPOTHESIS: The association between depression and insulin resistance has been investigated in only a few studies, with contradictory results reported. The aim of this study was to determine whether the association between symptoms of depression and insulin resistance varies across glucose...... established type 2 diabetes mellitus. Main outcome measures were insulin resistance defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and symptoms of depression using the Centre for Epidemiologic Studies Depression Scale (CES-D). RESULTS: In the total sample, we found a weak.......942). The association between depressive symptoms and insulin resistance was similar for men and women. CONCLUSIONS/INTERPRETATION: We found only weak associations between depressive symptoms and insulin resistance, which did not differ among different glucose metabolism subgroups or between men and women....

  10. Insulin Expression in Rats Exposed to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effects of cadmium exposure on insulin expression in rats. Methods Eighteen adult SD assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG (N-acyetyl-β-glucosaminidase) were determined. The gene expressions of metallothionein (MT) and insulin were also measured,and the oral glucose tolerance tests (OGTT) were carried out. Results The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas.not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression the change of the expression of insulin, MT-Ⅰ and MT-Ⅱ genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

  11. An Investigation of AdS2 Backreaction and Holography

    CERN Document Server

    Engelsöy, Julius; Verlinde, Herman

    2016-01-01

    We investigate a dilaton gravity model in AdS2 proposed by Almheiri and Polchinski and develop an 1D effective description in terms of a dynamical boundary time with a Schwarzian derivative action. We show that the effective model is equivalent to a 1D version of Liouville theory, and investigate its dynamics and symmetries via a standard canonical framework. We include the coupling to arbitrary conformal matter and analyze the effective action in the presence of possible sources. We compute commutators of local operators at large time separation, and match the result with the time shift due to a gravitational shockwave interaction. We study a black hole evaporation process and comment on the role of entropy in this model.

  12. Supersymmetry Properties of AdS Supergravity Backgrounds

    Science.gov (United States)

    Beck, Samuel; Gutowski, Jan; Papadopoulos, George

    2017-01-01

    Anti-de Sitter supergravity backgrounds are of particular interest in light of the AdS/CFT correspondence, which relates them to dual conformal field theories on the boundary of the anti-de Sitter space. We have investigated the forms of the supersymmetries these backgrounds preserve by solving the Killing spinor equations on the anti-de Sitter components of these spaces. We have found that a supersymmetric AdSn background necessarily preserves 2⌊n/2⌋ k supersymmetries for n 0 . Additionally, we have found that the Killing spinors of each background are exactly the zeroes of a Dirac-like operator constructed from the Killing spinor equations.

  13. Jet physics from static charges in AdS space

    Science.gov (United States)

    Chien, Yang-Ting; Schwartz, Matthew D.; Simmons-Duffin, David; Stewart, Iain W.

    2012-02-01

    Soft interactions with high-energy jets are explored in radial coordinates which exploit the approximately conformal behavior of perturbative gauge theories. In these coordinates, the jets, approximated by Wilson lines, become static charges in Euclidean AdS. The anomalous dimension of the corresponding Wilson line operator is then determined by the potential energy of the charges. To study these Wilson lines we introduce a “conformal gauge” which does not have kinetic mixing between radial and angular directions, and show that a number of properties of Wilson lines are reproduced through relatively simple calculations. For example, certain nonplanar graphs involving multiple Wilson lines automatically vanish. We also discuss the linear growth of the charges’ imaginary potential energy with separation, and a relationship between Wilson line diagrams and Witten diagrams.

  14. Jet Physics from Static Charges in AdS

    CERN Document Server

    Chien, Yang-Ting; Simmons-Duffin, David; Stewart, Iain W

    2011-01-01

    Soft interactions with high-energy jets are explored in radial coordinates which exploit the approximately conformal behavior of perturbative gauge theories. In these coordinates, the jets, approximated by Wilson lines, become static charges in Euclidean AdS. The anomalous dimension of the corresponding Wilson line operator is then determined by the potential energy of the charges. To study these Wilson lines we introduce a "conformal gauge" which does not have kinetic mixing between radial and angular directions, and show that a number of properties of Wilson lines are reproduced through relatively simple calculations. For example, certain non-planar graphs involving multiple Wilson lines automatically vanish. We also discuss the linear growth of the charges' imaginary potential energy with separation, and a relationship between Wilson line diagrams and Witten diagrams.

  15. Bootstrapping Pure Quantum Gravity in AdS3

    CERN Document Server

    Bae, Jin-Beom; Lee, Sungjay

    2016-01-01

    The three-dimensional pure quantum gravity with negative cosmological constant is supposed to be dual to the extremal conformal field theory of central charge $c=24k$ in two dimensions. We employ the conformal bootstrap method to analyze the extremal CFTs, and find numerical evidence for the non-existence of the extremal CFTs for sufficiently large central charge ($k \\ge 20$). We also explore near-extremal CFTs, a small modification of extremal ones, and find similar evidence for their non-existence for large central charge. This indicates, under the assumption of holomorphic factorization, the pure gravity in the weakly curved AdS$_3$ do not exist as a consistent quantum theory.

  16. Thermodynamics of charged Lovelock: AdS black holes

    Energy Technology Data Exchange (ETDEWEB)

    Prasobh, C.B.; Suresh, Jishnu; Kuriakose, V.C. [Cochin University of Science and Technology, Department of Physics, Cochin (India)

    2016-04-15

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime. (orig.)

  17. On Information Loss in AdS$_3$/CFT$_2$

    CERN Document Server

    Fitzpatrick, A Liam; Li, Daliang; Wang, Junpu

    2016-01-01

    We discuss information loss from black hole physics in AdS$_3$, focusing on two sharp signatures infecting CFT$_2$ correlators at large central charge $c$: 'forbidden singularities' arising from Euclidean-time periodicity due to the effective Hawking temperature, and late-time exponential decay in the Lorentzian region. We study an infinite class of examples where forbidden singularities can be resolved by non-perturbative effects at finite $c$, and we show that the resolution has certain universal features that also apply in the general case. Analytically continuing to the Lorentzian regime, we find that the non-perturbative effects that resolve forbidden singularities qualitatively change the behavior of correlators at times $t \\sim S_{BH}$, the black hole entropy. This may resolve the exponential decay of correlators at late times in black hole backgrounds. By Borel resumming the $1/c$ expansion of exact examples, we explicitly identify 'information-restoring' effects from heavy states that should correspo...

  18. Thermodynamics of charged Lovelock: AdS black holes

    Science.gov (United States)

    Prasobh, C. B.; Suresh, Jishnu; Kuriakose, V. C.

    2016-04-01

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime.

  19. Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes

    DEFF Research Database (Denmark)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J;

    2013-01-01

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization...

  20. Chromium-insulin reduces insulin clearance and enhances insulin signaling by suppressing hepatic insulin-degrading enzyme and proteasome protein expression in KKAy mice

    Directory of Open Access Journals (Sweden)

    Zhong Q Wang

    2014-07-01

    Full Text Available JDS-CRI-003 (CRI is a novel form of insulin that has been directly conjugated with chromium (Cr instead of zinc. Our hypothesis was that CRI enhances insulin’s effects by altering insulin degrading enzyme (IDE and proteasome enzymes. To test this hypothesis, we measured hepatic IDE content and proteasome parameters in a diabetic animal model. Male KKAy mice were randomly divided into three groups (n=8/group; Sham (saline, human insulin (Reg-In and chromium conjugated human insulin (CRI, respectively. Interventions were initiated at doses of 2 U insulin/kg body weight daily for eight-weeks. Plasma glucose and insulin were measured. Hepatic IDE, proteasome and insulin signaling proteins were determined by western blotting. Insulin tolerance tests at week 7 showed that both insulin treatments significantly reduced glucose concentrations and increased insulin levels compared with the Sham group, CRI significantly reduced glucose at 4 and 6 hours relative to Reg-In (P<0.05, suggesting the effects of CRI on reducing glucose last longer than Reg-In. CRI treatment significantly increased hepatic IRS-1 and Akt1 and reduced IDE, 20S as well as 19S protein abundance (P<0.01, P<0.05, and P<0.001, respectively, but Reg-In only significantly increased Akt1 (P<0.05. Similar results were also observed in Reg-In and CRI treated HepG2 cells. This study, for the first time, demonstrates that CRI reduces plasma insulin clearance by inhibition of hepatic IDE protein expression and enhances insulin signaling as well as prevents degradation of IRS-1 and IRS-2 by suppressing ubiquitin-proteasome pathway in diabetic mice.

  1. Insulin signaling pathways in lepidopteran steroidogenesis

    Directory of Open Access Journals (Sweden)

    Wendy eSmith

    2014-02-01

    Full Text Available Molting and metamorphosis are stimulated by the secretion of ecdysteroid hormones from the prothoracic glands. Insulin-like hormones have been found to enhance prothoracic gland activity, providing a mechanism to link molting to nutritional state. In silk moths (Bombyx mori, the prothoracic glands are directly stimulated by insulin and the insulin-like hormone bombyxin. Further, in Bombyx , the neuropeptide prothoracicotropic hormone (PTTH appears to act at least in part through the insulin-signaling pathway. In the prothoracic glands of Manduca sexta, while insulin stimulates the phosphorylation of the insulin receptor and Akt, neither insulin nor bombyxin II stimulate ecdysone secretion. Involvement of the insulin-signaling pathway in Manduca prothoracic glands was explored using two inhibitors of phosphatidylinositol-3-kinase (PI3K, LY294002 and wortmannin. PI3K inhibitors block the phosphorylation of Akt and 4EBP but have no effect on ecdysone secretion, or on the phosphorylation of the MAPkinase, ERK. Inhibitors that block phosphorylation of ERK, including the MEK inhibitor U0126, and high doses of the RSK inhibitor SL0101, effectively inhibit ecdysone secretion. The results highlight differences between the two lepidopteran insects most commonly used to directly study ecdysteroid secretion. In Bombyx, the PTTH and insulin-signaling pathways intersect; both insulin and PTTH enhance the phosphorylation of Akt and stimulate ecdysteroid secretion, and inhibition of PI3K reduces ecdysteroid secretion. By contrast, in Manduca, the action of PTTH is distinct from insulin. The results highlight species differences in the roles of translational regulators such as 4EBP, and members of the MAPkinase pathway such as ERK and RSK, in the effects of nutritionally-sensitive hormones such as insulin on ecdysone secretion and molting.

  2. Insulin Resistance: From Theory To Practice

    Directory of Open Access Journals (Sweden)

    Srinivas Kakkilaya Bevinje

    2006-07-01

    Full Text Available Insulin resistance is at the core of the well recognised metabolic syndrome and possibly many other ailments commonly seen in the modern society. While the quantification of insulin resistance remains a difficult task, the problems associated with it are increasing in epidemic proportions. Need of the hour therefore is to develop concise dietary and pharmacological guidelines for for prevention and management of insulin resistance

  3. Insulin resistance in women with hirsutism

    OpenAIRE

    Cebeci, Filiz; Onsun, Nahide; Mert, Meral

    2012-01-01

    Introduction There are still not enough data showing whether patients with idiopathic hirsutism (IH) also have insulin resistance. The association between polycystic ovary syndrome (PCOS) and insulin resistance is well documented in the literature, but the Rotterdam Consensus has concluded that principally obese women with PCOS should be screened for the metabolic syndrome. We intended to investigate the presence/absence of insulin resistance in non-obese women with hirsutism. Material and me...

  4. Low-dose insulin infusions in diabetic patients with high insulin requirements.

    Science.gov (United States)

    Dandona, P; Foster, M; Healey, F; Greenbury, E; Beckett, A G

    1978-08-01

    Six patients with high insulin requirements (range 120-3000 units daily) have been infused with much smaller doses (range 50-63 units daily) of insulin intravenously. All six maintained adequate glucose homoestasis on this regimen. It is suggested that subcutaneous tissue at the site of injection may alter insulin or impair its absorption. Insulin resistance in some patients may be due to these mechanisms.

  5. Insulin or insulin-like studies on unicellular organisms: a review

    OpenAIRE

    Alzira Martins Ferreira de Souza; López, Jorge A.

    2004-01-01

    This paper presents a review of studies about insulin and insulin-like substances in prokaryotes, eukaryotes and fungi have been published over the last two decades, constituting an updating of our previous review (1988) which included references to invertebrate insulin or insulin-like substances both in uni- and pluricellular Monera, Protoctista, Fungii and Animal species. This present article reviews experiments and evidence obtained using modern techniques in the understanding of molecule ...

  6. Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action

    OpenAIRE

    Eldar-Finkelman, Hagit; Krebs, Edwin G.

    1997-01-01

    The phosphorylation of insulin receptor substrate 1 (IRS-1) on tyrosine residues by the insulin receptor (IR) tyrosine kinase is involved in most of the biological responses of insulin. IRS-1 mediates insulin signaling by recruiting SH2 proteins through its multiple tyrosine phosphorylation sites. The phosphorylation of IRS-1 on serine/threonine residues also occurs in cells; however, the particular protein kinase(s) promoting this type of phosphorylation are unknown. Here we report that glyc...

  7. Altered insulin distribution and metabolism in type I diabetics assessed by (123I)insulin scanning

    Energy Technology Data Exchange (ETDEWEB)

    Hachiya, H.L.; Treves, S.T.; Kahn, C.R.; Sodoyez, J.C.; Sodoyez-Goffaux, F.

    1987-04-01

    Scintigraphic scanning with (/sup 123/I)insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of (/sup 123/I)insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of (/sup 123/I)insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of (/sup 123/I)insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of (/sup 123/I)insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of (/sup 123/I)insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of (/sup 123/I)insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of (123I)insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001).

  8. Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

    Institute of Scientific and Technical Information of China (English)

    Takumi; Kawaguchi; Michio; Sata

    2010-01-01

    Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indic...

  9. Insulin resistance in porphyria cutanea tarda.

    Science.gov (United States)

    Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

    1989-06-01

    It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

  10. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi

    2010-01-01

    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  11. Angiotensin and insulin resistance: conspiracy theory.

    Science.gov (United States)

    Townsend, Raymond R

    2003-04-01

    Resistance to the metabolic effects of insulin is a contender for the short list of major cardiovascular risk factors. Since the elements of the syndrome of insulin resistance were first articulated together in 1988, numerous epidemiologic investigations and treatment endeavors have established a relationship between the metabolic disarray of impaired insulin action and cardiovascular disease. Angiotensin II, the primary effector of the renin-angiotensin system, has also achieved a place in the chronicles of cardiovascular risk factors. Conspiracy mechanisms by which angiotensin II and insulin resistance interact in the pathogenesis of cardiovascular disease are reviewed, with particular attention to recent developments in this engaging area of human research.

  12. AdS/CFT Duality User Guide

    CERN Document Server

    Natsuume, Makoto

    2014-01-01

    This is the draft version of a textbook on "real-world" applications of the AdS/CFT duality for beginning graduate students in particle physics and for researchers in the other fields. The aim of this book is to provide background materials such as string theory, general relativity, nuclear physics, nonequilibrium physics, and condensed-matter physics as well as some key applications of the AdS/CFT duality in a single textbook. Contents: (1) Introduction, (2) General relativity and black holes, (3) Black holes and thermodynamics, (4) Strong interaction and gauge theories, (5) The road to AdS/CFT, (6) The AdS spacetime, (7) AdS/CFT - equilibrium, (8) AdS/CFT - adding probes, (9) Basics of nonequilibrium physics, (10) AdS/CFT - nonequilibrium, (11) Other AdS spacetimes, (12) Applications to quark-gluon plasma, (13) Basics of phase transition, (14) AdS/CFT - phase transition.

  13. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated t

  14. Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway.

    Science.gov (United States)

    Alonso-Castro, Angel Josabad; Zapata-Bustos, Rocio; Gómez-Espinoza, Guadalupe; Salazar-Olivo, Luis A

    2012-11-01

    Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.

  15. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

    Directory of Open Access Journals (Sweden)

    Tine N Vinther

    Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

  16. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    NARCIS (Netherlands)

    Bot, M.; Pouwer, F.; De Jonge, P.; Nolan, J. J.; Mari, A.; Hojlund, K.; Golay, A.; Balkau, B.; Dekker, J. M.

    2013-01-01

    Aim. This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods. The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

  17. Facilities Management and Added Value

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2010-01-01

    Aim: This paper aims to present different models of the concept of the added value of Facilities Management (FM), including the FM Value Map, which forms the basis of research group in EuroFM, and to present some of the results of this research collaboration. Approach and methodology: The paper...... on the aimed output) and the internal resource based view (with a focus on the input from FM and RE). Good relationship management and building on trust shows to be equally important as delivering the agreed services. In order to measure the multi-dimensional components of adding value both qualitative...... is based on literature reviews of the most influential journals within the academic fields of FM, Corporate Real Estate Management and Business to Business Marketing and discussions between participants of the research group working on a further exploration and testing of the FM Value Map. Conclusions...

  18. The PredictAD project

    DEFF Research Database (Denmark)

    Antila, Kari; Lötjönen, Jyrki; Thurfjell, Lennart;

    2013-01-01

    can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main...... candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials....

  19. Algorithms for intravenous insulin delivery.

    Science.gov (United States)

    Braithwaite, Susan S; Clement, Stephen

    2008-08-01

    This review aims to classify algorithms for intravenous insulin infusion according to design. Essential input data include the current blood glucose (BG(current)), the previous blood glucose (BG(previous)), the test time of BG(current) (test time(current)), the test time of BG(previous) (test time(previous)), and the previous insulin infusion rate (IR(previous)). Output data consist of the next insulin infusion rate (IR(next)) and next test time. The classification differentiates between "IR" and "MR" algorithm types, both defined as a rule for assigning an insulin infusion rate (IR), having a glycemic target. Both types are capable of assigning the IR for the next iteration of the algorithm (IR(next)) as an increasing function of BG(current), IR(previous), and rate-of-change of BG with respect to time, each treated as an independent variable. Algorithms of the IR type directly seek to define IR(next) as an incremental adjustment to IR(previous). At test time(current), under an IR algorithm the differences in values of IR(next) that might be assigned depending upon the value of BG(current) are not necessarily continuously dependent upon, proportionate to, or commensurate with either the IR(previous) or the rate-of-change of BG. Algorithms of the MR type create a family of IR functions of BG differing according to maintenance rate (MR), each being an iso-MR curve. The change of IR(next) with respect to BG(current) is a strictly increasing function of MR. At test time(current), algorithms of the MR type use IR(previous) and the rate-of-change of BG to define the MR, multiplier, or column assignment, which will be used for patient assignment to the right iso-MR curve and as precedent for IR(next). Bolus insulin therapy is especially effective when used in proportion to carbohydrate load to cover anticipated incremental transitory enteral or parenteral carbohydrate exposure. Specific distinguishing algorithm design features and choice of parameters may be important to

  20. Scattering States in AdS/CFT

    Energy Technology Data Exchange (ETDEWEB)

    Fitzpatrick, A.Liam; /Boston U.; Kaplan, Jared; /SLAC

    2012-02-14

    We show that suitably regulated multi-trace primary states in large N CFTs behave like 'in' and 'out' scattering states in the flat-space limit of AdS. Their transition matrix elements approach the exact scattering amplitudes for the bulk theory, providing a natural CFT definition of the flat space S-Matrix. We study corrections resulting from the AdS curvature and particle propagation far from the center of AdS, and show that AdS simply provides an IR regulator that disappears in the flat space limit.

  1. A novel surrogate index for hepatic insulin resistance.

    LENUS (Irish Health Repository)

    Vangipurapu, J

    2011-03-01

    In epidemiological and genetic studies surrogate indices are needed to investigate insulin resistance in different insulin-sensitive tissues. Our objective was to develop a surrogate index for hepatic insulin resistance.

  2. Preparation and Analysis of Acylated Insulin with Dehydrocholic Acid

    Institute of Scientific and Technical Information of China (English)

    Tao HUANG; Kai Xun HUANG

    2005-01-01

    Insulin was chemically modified with dehydrocholic acid without the use of protecting agents and the main monoacylated insulin. ε-NB29-Dehydrocholyl insulin was obtained selectively and analyzed by PAGE, HPLC and MALDI-TOF-MS.

  3. Towards Timelike Singularity via AdS Dual

    CERN Document Server

    Bhowmick, Samrat

    2016-01-01

    It is well known that Kasner geometry with spacelike singularity can be extended to bulk AdS-like geometry, furthermore one can study field theory on this Kasner space via its gravity dual. In this paper, we show that there exists a Kasner-like geometry with timelike singularity for which one can construct a dual gravity description. We then study various minimal surfaces including spacelike geodesics. Finally, we compute correlators of highly massive operators in the boundary field theory with a geodesic approximation.

  4. Holography in 3D AdS gravity with torsion

    CERN Document Server

    Blagojević, Milutin; Miskovic, Olivera; Olea, Rodrigo

    2013-01-01

    Basic aspects of the AdS/CFT correspondence are studied in the framework of 3-dimensional gravity with torsion. After choosing a consistent holographic ansatz, we formulate an improved approach to the Noether--Ward identities for the boundary theory. The method is applied first to the topological Mielke--Baekler model, and then to the more interesting (parity-preserving) 3-dimensional gravity with propagating torsion. In both cases, we find the finite holographic energy-momentum and spin currents and obtain the associated (anomalous) Noether--Ward identities.

  5. Canonical energy and hairy AdS black holes

    CERN Document Server

    Hyun, Seungjoon; Yi, Sang-Heon

    2016-01-01

    We propose the modified version of the canonical energy which was introduced originally by Hollands and Wald. Our construction depends only on the Euler-Lagrange expression of the system and thus is independent of the ambiguity in the Lagrangian. After some comments on our construction, we briefly mention on the relevance of our construction to the boundary information metric in the context of the AdS/CFT correspondence. We also study the stability of three-dimensional hairy extremal black holes by using our construction.

  6. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U

    2012-01-01

    . However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood...... accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated...... with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP...

  7. Streptozotocin diabetes and insulin resistance impairment of spermatogenesis in adult rat testis: central vs. local mechanism.

    Science.gov (United States)

    Arikawe, A P; Oyerinde, A; Olatunji-Bello, I I; Obika, L F O

    2012-12-18

    Mammalian reproduction is dynamically regulated by the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are synthesized in the pituitary gland following stimulation by the gonadotropin-releasing hormone (GnRH) and act by stimulating steroid production and gametogenesis in both males and females. Male adult Sprague-Dawley rats (120 - 140 g) were randomly divided into 7 groups. Group 1 > Control group; fed on normal rat pellets. Group 2 > Streptozotocin group; received a single dose IP injection of streptozotocin 45 mg/kg BW in Na+ citrate buffer pH 4.5. Group 3 > Streptozotocin-insulin treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with insulin sub-cutaneously. Group 4 > Streptozotocin-ginger treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with 500 mg/Kg Ginger extract orally. Group 5 > Insulin resistant group; fed ad libitum on a special diet containing 25% fructose mixed with 75% normal rat chow (w/w). Group 6 > Insulin resistant-pioglitazone treated group; fed ad libitum on a special diet as in group 5 above and treated with Pioglitazone 15 mg/kg orally. Group 7 > Insulin resistant-ginger treated group; fed ad libitum on a special diet as in group 4 above, and also treated with 500 mg/Kg Ginger extract orally. Hormonal and tissue biochemistry analyses revealed that both central and local mechanisms are implicated in the impairment of spermatogenesis by diabetes but the hypothalamo-pituitary testicular axis alteration might not likely have a major impact as the local defect on steroidogenesis in the testis. This local defect could also predispose to male hypogonadism, i.e. failure of gonadal function.

  8. Use of a small peptide fragment as an inhibitor of insulin fibrillation process: a study by high and low resolution spectroscopy.

    Directory of Open Access Journals (Sweden)

    Victor Banerjee

    Full Text Available A non-toxic, nine residue peptide, NIVNVSLVK is shown to interfere with insulin fibrillation by various biophysical methods. Insulin undergoes conformational changes under certain stress conditions leading to amyloid fibrils. Fibrillation of insulin poses a problem in its long-term storage, reducing its efficacy in treating type II diabetes. The dissociation of insulin oligomer to monomer is the key step for the onset of fibrillation. The time course of insulin fibrillation at 62°C using Thioflavin T fluorescence shows an increase in the lag time from 120 min without peptide to 236 min with peptide. Transmission electron micrographs show branched insulin fibrils in its absence and less inter-fibril association in its presence. Upon incubation at 62°C and pH 2.6, insulin lost some α-helical structure as seen by Fourier transformed infra-red spectroscopy (FT-IR, but if the peptide is added, secondary structure is almost fully maintained for 3 h, though lost partially at 4 h. FT-IR spectroscopy also shows that insulin forms the cross beta structure indicative of fibrils beyond 2 h, but in the presence of the peptide, α-helix retention is seen till 4 h. Both size exclusion chromatography and dynamic light scattering show that insulin primarily exists as trimer, whose conversion to a monomer is resisted by the peptide. Saturation transfer difference nuclear magnetic resonance confirms that the hydrophobic residues in the peptide are in close contact with an insulin hydrophobic groove. Molecular dynamics simulations in conjunction with principal component analyses reveal how the peptide interrupts insulin fibrillation. In vitro hemolytic activity of the peptide showed insignificant cytotoxicity against HT1080 cells. The insulin aggregation is probed due to the inter play of two key residues, Phe(B24 and Tyr(B26 monitored from molecular dynamics simulations studies. Further new peptide based leads may be developed from this nine residue peptide.

  9. Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes

    DEFF Research Database (Denmark)

    Niskanen, Leo; Leiter, Lawrence A; Franek, Edward;

    2012-01-01

    Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30)....

  10. The Clinical Application and Mechanism of Weight Reduction of Insulin Detemir%地特胰岛素减少体重增加的临床应用与机制探讨

    Institute of Scientific and Technical Information of China (English)

    杨彩娴

    2016-01-01

    2型糖尿病与肥胖症近年来都呈明显高发态势,糖尿病患者合并肥胖比例亦明显增加。肥胖不仅增加糖尿病患病风险,同时增加了患者血糖达标难度。因此,在选择降糖药物时必须关注降糖药物本身对体重的影响,尤其是使用胰岛素方案时尽量选择对体重影响小的药物。地特胰岛素是长效胰岛素类似物,体重增加幅度小于中效胰岛素及甘精胰岛素。研究发现,地特胰岛素减少体重增加主要涉及以下三方面机制:减少机体能量摄入;更多通过血脑屏障,作用于下丘脑等摄食相关区域,减少食物摄入;相对恢复肝脏/外周组织胰岛素浓度梯度,在外周组织促合成作用相对减弱。总之对于糖尿病患者采用胰岛素治疗,应合理选择胰岛素种类及方案,避免体重过度增加。%Type 2 diabetes mellitus and obesity have showed a high incidence in recent years, the proportion of diabetic patients with obesity also increased significantly. Obesity not only increases the risk of diabetes, but also increases the difficulty of blood glucose target. Therefore, we must pay attention to the effects of antidiabetic drugs on body weight, especially when using insulin therapy, we should choose the drugs which have less effect on the body weight. Insulin detemir is long-acting insulin analogue, its weight gain is significantly lower than intermediate-acting insulin and insulin glargine. Study found that insulin detemir reduce weight gain involves three mechanisms: reduce the intake of the body's energy; more through the blood-brain barrier, in the region of hypothalamus feeding so as to reduce food intake; relatively recover the liver/peripheral tissue insulin concentration gradient and relatively weaken the synthesis in the peripheral tissues. In conclusion, when we choose insulin therapy for patients with diabetes mellitus, the type of insulin should be chosen rationally to avoid

  11. Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

    Science.gov (United States)

    Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

    2009-01-01

    Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

  12. On modular properties of the AdS3 CFT

    CERN Document Server

    Baron, Walter

    2010-01-01

    We study modular properties of the AdS3 WZNW model. Although the Euclidean partition function is modular invariant, the characters on the Euclidean torus are ill-defined and their modular transformations are unknown. We reconsider the characters defined on the Lorentzian torus, focusing on their structure as distributions. We find a generalized S matrix, depending on the sign of the real modular parameters, which has two diagonal blocks and one off-diagonal block, mixing discrete and continuous representations, that we fully determine. We then explore the relations among the modular transformations, the fusion algebra and the boundary states. We explicitly construct Ishibashi states for the maximally symmetric D-branes and show that the generalized S matrix defines the one-point functions associated to point-like and H2 branes as well as the fusion rules of the degenerate representations of SL(2,R) appearing in the open string spectrum of the point-like D-branes, through a generalized Verlinde theorem.

  13. Insulin resistance in H pylori infection and its association with oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Mehmet Aslan; Mehmet Horoz; Yasar Nazligul; Cengiz Bolukbas; F Fusun Bolukbas; Sahbettin Selek; Hakim Celik; Ozcan Erel

    2006-01-01

    AIM:To determine the insulin resistance (IR) and oxidative status in H pylori infection and to find out if there is any relationship between these parameters and insulin resistance.METHODS:Fifty-five H pylori positive and 48 H pylori negative patients were enrolled. The homeostasis model assessment (HOMA) was used to assess insulin resistance. Serum total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined in all subjects.RESULTS:The total antioxidant capacity was significantly lower in H pylori positive group than in H pylori negative group (1.36 ± 0.33 and 1.70 ± 0.50,respectively; P < 0.001), while the total oxidant status and oxidative stress index were significantly higher in H pylori positive group than in H pylori negative group (6.79 ± 3.40 and 5.08 ± 0.95, and 5.42 ± 3.40 and 3.10± 0.92, respectively; P < 0.001). Insulin resistance was significantly higher in H pylori positive group than in H pylori negative group (6.92 ± 3.86 and 3.61 ± 1.67, respectively; P < 0.001). Insulin resistance was found to be significantly correlated with total antioxidant capacity (r= -0.251, P < 0.05), total oxidant status (r = 0.365, P <0.05), and oxidative stress index (r = 0.267, P < 0.05).CONCLUSION: Insulin resistance seems to be associated with increased oxidative stress in H pylori infection.Further studies are needed to clarify the mechanisms underlying this association and elucidate the effect of adding antioxidant vitamins to H pylori eradication therapy on insulin resistance during H pylori infection.

  14. The ADS All Sky Survey

    Science.gov (United States)

    Goodman, Alyssa

    We will create the first interactive sky map of astronomers' understanding of the Universe over time. We will accomplish this goal by turning the NASA Astrophysics Data System (ADS), widely known for its unrivaled value as a literature resource, into a data resource. GIS and GPS systems have made it commonplace to see and explore information about goings-on on Earth in the context of maps and timelines. Our proposal shows an example of a program that lets a user explore which countries have been mentioned in the New York Times, on what dates, and in what kinds of articles. By analogy, the goal of our project is to enable this kind of exploration-on the sky-for the full corpus of astrophysical literature available through ADS. Our group's expertise and collaborations uniquely position us to create this interactive sky map of the literature, which we call the "ADS All-Sky Survey." To create this survey, here are the principal steps we need to follow. First, by analogy to "geotagging," we will "astrotag," the ADS literature. Many "astrotags" effectively already exist, thanks to curation efforts at both CDS and NED. These efforts have created links to "source" positions on the sky associated with each of the millions of articles in the ADS. Our collaboration with ADS and CDS will let us automatically extract astrotags for all existing and future ADS holdings. The new ADS Labs, which our group helps to develop, includes the ability for researchers to filter article search results using a variety of "facets" (e.g. sources, keywords, authors, observatories, etc.). Using only extracted astrotags and facets, we can create functionality like what is described in the Times example above: we can offer a map of the density of positions' "mentions" on the sky, filterable by the properties of those mentions. Using this map, researchers will be able to interactively, visually, discover what regions have been studied for what reasons, at what times, and by whom. Second, where

  15. Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus. A weight reduction-exercise-oral agent approach.

    Science.gov (United States)

    Lucas, C P; Patton, S; Stepke, T; Kinhal, V; Darga, L L; Carroll-Michals, L; Spafford, T R; Kasim, S

    1987-09-18

    Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular

  16. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease

    Science.gov (United States)

    Our aim was to investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) a...

  17. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    attenuates arsenic-induced diabetes in mice. ► Encapsulated insulin acts effectively at nearly 10 fold lesser dose than insulin. ► Injection route is more effective than oral administration route. ► Nano-insulin can cross blood–brain barrier with added physiological implications. ► Nano-insulin acts mainly through regulation of mitochondrial signaling cascade.

  18. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    Directory of Open Access Journals (Sweden)

    Mathew John

    2016-01-01

    Full Text Available The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2 inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in terms of weight loss and reduction of blood pressure in addition to improvements in glycemic control. Further, one of the SGLT2 inhibitors, empagliflozin has proven benefits in reducing adverse cardiovascular (CV outcomes in a CV outcome trial. Adding SGLT2 inhibitors to insulin in subjects with type 2 diabetes produced favorable effects on glycemic control without the weight gain and hypoglycemic risks associated with insulin therapy. The general risks of increased genital mycotic infections, urinary tract infections, volume, and osmosis-related adverse effects in these subjects were similar to the pooled data of individual SGLT2 inhibitors. There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or is prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis.

  19. Two Cases of Allergy to Insulin in Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Gi Jun Kim

    2015-09-01

    Full Text Available Allergic reaction to insulin is uncommon since the introduction of human recombinant insulin preparations and is more rare in pregnant than non-pregnant females due to altered immune reaction during pregnancy. Herein, we report two cases of allergic reaction to insulin in gestational diabetes that were successfully managed. One case was a 33-year-old female using isophane-neutral protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea, cough, urticaria and itching sensation at the sites of insulin injection immediately after insulin administration. We discontinued insulin therapy and started oral hypoglycemic agents with metformin and glibenclamide. The other case was a 32-year-old female using insulin lispro and insulin detemer. She experienced pruritus and burning sensation and multiple nodules at the sites of insulin injection. We changed the insulin from insulin lispro to insulin aspart. Assessments including immunoglobulin E (IgE, IgG, eosinophil, insulin antibody level and skin biopsy were performed. In the two cases, the symptoms were resolved after changing the insulin to oral agents or other insulin preparations. We report two cases of allergic reaction to human insulin in gestational diabetes due to its rarity.

  20. Membrane topology of insulin receptors reconstituted into lipid vesicles

    DEFF Research Database (Denmark)

    Tranum-Jensen, Jørgen; Christiansen, K.; Carlsen, Jens;

    1994-01-01

    Anatomy, insulin receptors, membrane reconstitution, electron microscopy, quaternary structure, immunogold labeling......Anatomy, insulin receptors, membrane reconstitution, electron microscopy, quaternary structure, immunogold labeling...

  1. [B17-D-leucine]insulin and [B17-norleucine]insulin: synthesis and biological properties.

    Science.gov (United States)

    Knorr, R; Danho, W; Büllesbach, E E; Gattner, H G; Zahn, H; King, G L; Kahn, C R

    1983-11-01

    The chemical synthesis of two porcine insulin analogues is described. Leucine in position B17 of the native molecule was substituted by its D-enantiomer and by L-norleucine, respectively. Both B-chain derivatives were synthesized by fragment condensation and purified as di-S-sulphonates by gel filtration followed by ion exchange chromatography on SP-Sephadex at pH3. Combination with native sulphhydryl A-chain yielded [DLeuB17]insulin and [NleB17]insulin. Both insulin analogues were isolated by gel filtration followed by ion exchange chromatography on CM-cellulose at pH 4.0. Biological activities of the analogues were determined relative to native pork insulin: 1) glucose oxidation in rat epididymal adipocytes was 6% for [DLeuB17]insulin and 16% for [NleB17]insulin, 2) receptor-binding affinity tested with cultured human fibroblasts and with rat adipocytes was 3% for [DLeuB17]insulin and 26% for [NleB17]insulin, and 3) thymidine incorporation into DNA of human fibroblasts was 35% for [DLeuB17]insulin and 100% for [NleB17]insulin.

  2. A paradox: Insulin inhibits expression and secretion of resistin which induces insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Feng Liu; Mei Guo; Rong-Hua Chen; Xi-Rong Guo; Hong-Qi Fan; Jie Qiu; Bin Wang; Min Zhang; Nan Gu; Chun-Mei Zhang; Li Fei; Xiao-Qing Pan

    2008-01-01

    AIM:To confirm whether insulin regulates resistin expression and secretion during differentiation of 3T3-L1 preadipocytes and the relationship of resistin with insulin resistance both in vivo and in vitro. METHODS: Supernatant resistin was measured during differentiation of 3T3-L1 preadipocytes. L6 rat myoblasts and hepatoma cell line H4IIE were used to confirm the cellular function of resistin. Diet-induced obese rats were used as an insulin resistance model to study the relationship of resistin with insulin resistance.RESULTS: Resistin expression and secretion were enhanced during differentiation 3T3-L1 preadipocytes. This cellular differentiation stimulated resistin expression and secretion, but was suppressed by insulin. Resistin also induced insulin resistance in H4IIE hepatocytes and L6 myoblasts. In diet-induced obese rats, serum resistin levels were negatively correlated with insulin sensitivity,but not with serum insulin. CONCLUSION: Insulin can inhibit resistin expression and secretion in vitro, but insulin is not a major regulator of resistin in vivo. Fat tissue mass affects insulin sensitivity by altering the expression and secretion of resistin.

  3. Insulin sensitivity and hemodynamic responses to insulin in Wistar-Kyoto and spontaneously hypertensive rats.

    Science.gov (United States)

    Pître, M; Nadeau, A; Bachelard, H

    1996-10-01

    The insulin-mediated vasodilator effect has been proposed as an important physiological determinant of insulin action on glucose disposal in normotensive humans. The present study was designed to further examine the acute regional hemodynamic effects of insulin in different vascular beds and to explore the relationships between insulin vascular effects and insulin sensitivity during euglycemic hyperinsulinemic clamps in conscious normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and regional blood flows. In WKY rats, the euglycemic infusion of insulin (4 and 16 mU.kg-1.min-1) causes vasodilations in renal and hindquarter vascular beds but no changes in mean blood pressure, heart rate, or superior mesenteric vascular conductance. In contrast, in SHR, the same doses of insulin produce vasoconstrictions in superior mesenteric and hindquarter vascular beds and, at high doses, increase blood pressure. Moreover, at the lower dose of insulin tested, we found a reduction in the insulin sensitivity index in the SHR compared with the WKY rats. The present findings provide further evidence for an association between insulin sensitivity and insulin-mediated hemodynamic responses.

  4. Peroral insulin delivery : new concepts and excipients

    NARCIS (Netherlands)

    Sadeghi, Assal M.M.

    2008-01-01

    A number of chitosan derivatives were synthesized and compared to the previously synthesized derivatives for their permeation enhancing activity. Using these derivatives insulin nanoparticles were prepared and their effect was compared to the free polymer and insulin in Caco-2 cells. The results sug

  5. Factoren die de insuline gevoeligheid beinvloeden

    NARCIS (Netherlands)

    Numan, Witte

    1980-01-01

    Volgens de gegevens uit de literatuur die in hoofdstuk 1 worden besproken, is glucose de belangrijkste prikkel voor de insuline afgifte. Na orale toediening van glucose worden hogere insuline spiegels gevonden dan na het toedienen van glucose intraverneus. Het gastric inhibitory polypeptide is van d

  6. Considerations in biosimilar insulin device development

    Directory of Open Access Journals (Sweden)

    Fry AR

    2016-02-01

    Full Text Available Andy R Fry,1 Andrew J Krentz,2 Marcus Hompesch2 1Team Consulting Limited, Ickleton, Cambridge, UK; 2Profil Institute for Clinical Research, Chula Vista, CA, USA Abstract: Biosimilar insulins, also known as follow-on biologics, are modifications of an originator insulin that are intended to be clinically equivalent to the licensed product. For injectable insulins, or other peptides used in the management of diabetes, regular use of an insulin pen injector or other device to administer therapy is part of the patient's self-management regimen. By definition, the biosimilar product should have comparable pharmacokinetic and pharmacodynamic properties to the reference product. However, the device is the initial interaction for the patient rather than the product contained within. We consider the regulatory aspects of insulin device development. The options for manufacturers bringing a biosimilar insulin to market, including whether to outsource development of delivery devices, are explored. The structure of a device development program is outlined and issues of accuracy, safety, ease of use, and attractiveness of modern insulin delivery devices are discussed. Keywords: biosimilar insulin, delivery devices, diabetes mellitus 

  7. Diclofenac derivatives with insulin-sensitizing activity

    Institute of Scientific and Technical Information of China (English)

    Jian Ta Wang; Ying Wang; Ji Quan Zhang; Xing Cui; Yi Zhang; Gao Feng Zhu; Lei Tang

    2011-01-01

    A series of diclofenac derivatives were synthesized. The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3-L1 cells. The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drag rosiglitazone.

  8. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

    2013-01-01

    Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

  9. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

    2003-01-01

    Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown.......Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown....

  10. Selective insulin resistance in hepatocyte senescence

    Energy Technology Data Exchange (ETDEWEB)

    Aravinthan, Aloysious [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Challis, Benjamin [Institute of Metabolic Sciences, University of Cambridge, Cambridge (United Kingdom); Shannon, Nicholas [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Hoare, Matthew [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Heaney, Judith [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Foundation for Liver Research, Institute of Hepatology, London (United Kingdom); Alexander, Graeme J.M., E-mail: gja1000@doctors.org.uk [Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Cambridge (United Kingdom)

    2015-02-01

    Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied in three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.

  11. Resolution of lipohypertrophy following change of short-acting insulin to insulin lispro (Humalog).

    Science.gov (United States)

    Roper, N A; Bilous, R W

    1998-12-01

    Lipohypertrophy as a local complication of insulin therapy is well recognized. Despite improvements in insulin purity and the introduction of recombinant human insulin its prevalence has remained high. Rotation of injection sites can reduce the frequency of the problem but does not abolish it. The importance of this complication is not only cosmetic but also in its impact on insulin absorption, and hence glycaemic control. We report a patient who had intractable lipohypertrophy with human recombinant insulin but experienced no such problem when converted onto the insulin analogue lispro. We suggest that the faster speed of absorption of insulin lispro may lead to less hypertrophic stimulation of subcutaneous adipocytes. This difference may be clinically useful in susceptible individuals.

  12. Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion.

    Science.gov (United States)

    Salunkhe, Vishal A; Mollet, Inês G; Ofori, Jones K; Malm, Helena A; Esguerra, Jonathan L S; Reinbothe, Thomas M; Stenkula, Karin G; Wendt, Anna; Eliasson, Lena; Vikman, Jenny

    2016-08-01

    Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca(2+) signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.

  13. Insulin

    Science.gov (United States)

    ... your diabetes medicines. Be active and get exercise. Dance, take a walk, or join an exercise class. Check with your doctor about safe ways to be more active. Monitor your overall mental and physical health. Work with your health care team to keep ...

  14. Insulin inhalation for diabetic patients: Nursing considerations

    Directory of Open Access Journals (Sweden)

    Hanan Mohammed Mohammed

    2016-04-01

    Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

  15. Insulin release by glucagon and secretin

    DEFF Research Database (Denmark)

    Kofod, Hans; Andreu, D; Thams, P

    1988-01-01

    Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated th...... potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different.......Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated...

  16. [Intensified insulin treatment is cost-effective].

    Science.gov (United States)

    Reichard, P; Alm, C; Andersson, E; Wärn, I; Rosenqvist, U

    1999-01-20

    Both the Diabetes Control and Complications Trial (DCCT) in USA/Canada, and Stockholm Diabetes Intervention Study (SDIS) showed intensified insulin treatment and reduced glycaemia to prevent complications in patients with insulin-dependent (type I) diabetes mellitus. In the DCCT, the intensified treatment was considered cost-effective. In the SDIS, investigation of the direct increase in costs due to the intensified insulin treatment showed the saving in direct costs due to the reduction in photocoagulation requirements, and in the prevalence of renal insufficiency and of amputation, to correspond to 10 years' intensive insulin treatment. Thus, as intensified insulin treatment in type I diabetes reduces direct suffering at a low cost, it may be regarded as 'evidence-based' and mandatory.

  17. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    Lan-fang Li; Jian Li

    2007-01-01

    Many studies on oxidative stress, insulin resistance, and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states. Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress. And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance. However, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications. Furthermore, it appears that oxidative stress is only one of the factors contributing to diabetic complications. Thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

  18. Agonism and antagonism at the insulin receptor

    DEFF Research Database (Denmark)

    Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia;

    2012-01-01

    Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new...... insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been...... shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B'29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR...

  19. Molecular basis for insulin fibril assembly

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, Magdalena I.; Sievers, Stuart A.; Sawaya, Michael R.; Wall, Joseph S.; Eisenberg, David; (HHMI); (BNL)

    2009-12-01

    In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that the segment of the insulin B-chain with sequence LVEALYL is the smallest segment that both nucleates and inhibits the fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting that this segment is central to the cross-{beta} spine of the insulin fibril. In isolation from the rest of the protein, LVEALYL forms microcrystalline aggregates with fibrillar morphology, the structure of which we determined to 1 {angstrom} resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated {beta}-sheets, each pair displaying the dry steric zipper interface typical of amyloid-like fibrils. This structure leads to a model for fibrils of human insulin consistent with electron microscopic, x-ray fiber diffraction, and biochemical studies.

  20. Inhaled insulin--does it become reality?

    Science.gov (United States)

    Siekmeier, R; Scheuch, G

    2008-12-01

    After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing