WorldWideScience

Sample records for adding insulin glargine

  1. [Medication of the month. Insulin glargine (Lantus)].

    Scheen, A J

    2004-02-01

    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 glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy. PMID:15112902

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

    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...

  3. Insulin glargine: pharmacokinetic and pharmacodynamic basis of clinical effect

    Vadim Valeryevich Klimontov

    2014-10-01

    Full Text Available Glargine became the first long-acting insulin analogue. Glargine was designed to meet basal insulin requirements throughout the day with a single injection. Pharmacokinetics of insulin glargine is characterized by biotransformation into metabolites M1 and M2 that transforms the B chain of glargine so it is similar to the B chain of human insulin. Plasma concentrations of active M1 and M2 metabolites have no pronounced peaks during the day, resulting in lower glucose variability and hypoglycaemia risk when compared with NPH insulin. The metabolic activities of M1 and M2 metabolites are similar to the effect of glargine, whereas the mitogenic effects of these metabolites do not exceed the effect of human insulin. Insulin glargine shows a higher affinity for the insulin-like growth factor-1 (IGF-1 receptor when compared with human insulin. Glargine has no proliferative effect in vivo owing to its rapid conversion into metabolites. Pharmacokinetic and pharmacodynamic variability of glargine is comparable to other insulins. These characteristics are important for the clinical efficacy and safety of glargine.

  4. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand;

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  5. Insulin Glargine: a review 8 years after its introduction.

    Goykhman, Stanislav; Drincic, Andjela; Desmangles, Jean Claude; Rendell, Marc

    2009-03-01

    Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The principal advantage of insulin Glargine over neutral protamine Hagedorn (NPH) insulin is in a lower frequency of hypoglycemic reactions, thus affording improved safety. It is used in both type 1 and type 2 diabetes, usually as a single daily dose. In type 2 patients, it is often the first insulin introduced as a single daily dose. Although insulin Glargine is typically administered as a single nighttime dose, it can be given in the morning or at any other time convenient for the patient. In labile type 1 diabetes, it is often most effective given as two daily injections. In obese, insulin-resistant patients, it may be best to administer insulin Glargine in two separate doses, owing to the high volumes of injected insulin required. Insulin Glargine does not treat postprandial hyperglycemia. It is necessary to supplement with short-acting insulin at mealtimes to control glucose surges after meals. Insulin Glargine is effective in hospitalized and postsurgical patients on account of its lack of pronounced insulin peaks and long duration of action. Although there is considerable use of Glargine in pregnant diabetic women, there is no definitive study to confirm its benefits. Insulin Glargine is thought to coprecipitate supplementary short-acting insulins when co-administered in the same syringe. Therefore, more injections are typically needed in the usual treatment regimen for insulin requiring diabetes. In many cases, constant basal insulin levels may be achieved with multiple overlapping doses of NPH insulin given together with short-acting insulin at mealtimes. Such a therapy may be less costly, but the major advantage of

  6. Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

    Stürmer, Til; Marquis, M. Alison; Zhou, Haibo; Meigs, James B; Lim, Soo; Blonde, Lawrence; MacDonald, Eileen; Wang, Ray; LaVange, Lisa M.; Pate, Virginia; Buse, John B.

    2013-01-01

    OBJECTIVE To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN AND METHODS We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second pre...

  7. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes

    Rodbard, H W; Cariou, B; Zinman, B;

    2013-01-01

    The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes.......The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes....

  8. Insulin glargine: an updated review of its use in the management of diabetes mellitus.

    Dunn, Christopher J; Plosker, Greg L; Keating, Gillian M; McKeage, Kate; Scott, Lesley J

    2003-01-01

    Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. 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 from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine

  9. Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

    Pešić Milica

    2007-01-01

    Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  10. Insulin glargine and cancer risk in patients with diabetes: a meta-analysis.

    Xulei Tang

    Full Text Available AIM: The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence. METHODS: All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs with corresponding 95% confidence interval (CI were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence. Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence. Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer. CONCLUSIONS: Results from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

  11. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report.

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira; So, Tsz-Yin

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID:26997933

  12. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with Type 1 diabetes

    Ashwell , SG; Stephens, JW; Witthaus, E; Home, PD; Bradley, Clare

    2008-01-01

    OBJECTIVE— The purpose of this study was to compare quality of life and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens. RESEARCH DESIGN AND METHODS— As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twi...

  13. Spotlight on insulin glargine in type 1 and 2 diabetes mellitus.

    McKeage, Kate; Goa, Karen L

    2002-01-01

    Insulin glargine is a recombinant human insulin analog produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analog provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated hemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycemia, especially nocturnal hypoglycemia, with insulin glargine compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic. In conclusion, insulin glargine once a day provides basal control of glycemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long-term, well designed trials insulin glargine once daily

  14. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira; So, Tsz-Yin

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insu...

  15. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine.

    Belhekar, Mahesh N; Pai, Sarayu; Tayade, Parimal; Dalwadi, Pradip; Munshi, Renuka; Varthakavi, Prema

    2015-01-01

    Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control. PMID:25878390

  16. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine

    Mahesh N Belhekar

    2015-01-01

    Full Text Available Insulin is an important agent for the treatment of diabetes mellitus (DM. Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1 hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control.

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

    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.

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

    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.

  19. Insulin degludec does not increase antibody formation versus insulin glargine: an evaluation of phase IIIa trials.

    Vora, J; Seufert, J; Solberg, H; Kinduryte, O; Johansen, T; Hollander, P

    2016-07-01

    We examined insulin antibody formation in patients with type 1 (T1D) or type 2 diabetes (T2D) treated with once-daily insulin degludec (IDeg) or insulin glargine (IGlar) to evaluate the impact of antibody formation on efficacy and safety. Insulin antibodies were measured using subtraction radioimmunoassays in six phase IIIa clinical trials using IDeg (n = 2250) and IGlar (n = 1184). Spearman's correlation coefficient was used to evaluate associations between cross-reacting antibodies and change from baseline glycated haemoglobin (HbA1c) and insulin dose. IDeg- and IGlar-specific antibodies remained low [correlation coefficients between insulin antibody levels and change in HbA1c or insulin dose were low in both treatment groups. No clinically meaningful differences in adverse event (AE) rates were observed in patients with >10% B/T or without an absolute increase in antibodies cross-reacting with human insulin. IDeg treatment resulted in few immunogenic responses in patients with T1D and T2D; antibody formation was not associated with change in HbA1c, insulin dose or rates of AEs. PMID:26663320

  20. Cancer Risk Associated with Insulin Glargine among Adult Type 2 Diabetes Patients – A Nationwide Cohort Study

    Chang, Chia-Hsuin; Toh, Sengwee; Lin, Jou-Wei; Chen, Shu-Ting; Kuo, Chuei-Wen; Chuang, Lee-Ming; Lai, Mei-Shu

    2011-01-01

    Background Preclinical and observational studies raise the concern about the safety of insulin glargine in terms of cancer initiation and promotion. This study is designed to examine cancer incidence associated with use of insulin glargine vs. intermediate/long-acting human insulin (HI). Methodology A retrospective cohort study using the Taiwan National Health Insurance claims database was conducted to identify adult patients with type 2 diabetes mellitus and without a history of cancer who i...

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

    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.

  2. A Comparison of Costs among Patients with Type 2 Diabetes Mellitus Who Initiated Therapy with Exenatide or Insulin Glargine

    Derek Misurski; Lage, Maureen J; Rosalind Fabunmi; Boye, Kristina S.

    2009-01-01

    Background: Exenatide (Byetta) and insulin glargine (Lantus) are antidiabetic agents that are typically used after lack of response to an oral antidiabetic agent(s). Although previous research has examined the impact of these medications on glycaemic control, there is little information about the relative costs associated with the medications. Objective: To compare costs among patients with type 2 diabetes mellitus treated with exenatide or insulin glargine from a US third-party payer perspec...

  3. Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database

    Blin, P.; Lassalle, R.; Dureau-Pournin, C.; Ambrosino, B.; Bernard, M. A.; Abouelfath, A.; Gin, H; Le Jeunne, C; Pariente, A.; Droz, C.; Moore, N

    2012-01-01

    Aims/hypothesis Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. Methods We used Cox proportional hazards time-dependent models that were stratified on propensit...

  4. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine

    Strandberg, Arto Y.; Hoti, Fabian J.; Strandberg, Timo E.; Christopher, Solomon; Haukka, Jari; Korhonen, Pasi

    2016-01-01

    Background Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown. Objective To estimate the differences in all-cause and cause-specific mo...

  5. MEK1 and MEK2 differentially regulate human insulin-and insulin glargine-induced human bladder cancer T24 cell proliferation

    LIU Shan-ying; LIANG Ying; LIN Tian-xin; SU Fang; LIANG Wei-wen; Uwe Heemann; LI Yan

    2012-01-01

    Background Increased risk of bladder cancer has been reported in diabetic patients.This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin-and insulin glargine-induced proliferation of human bladder cancer T24 cells.Methods In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2),with or without addition of insulin or glargine,T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay.Protein expression of MEK2,phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.Results T24 cell proliferation was promoted by PD98059 at 5-20 μmol/L,inhibited by siMEK2 at 25-100 nmol/L.PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2.Insulin-and glargine-induced T24 cell proliferation was enhanced by PD98059,suppressed while not blocked by siMEK2.Insulin-and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment,whereas activation of Akt was not affected.Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin-and insulin glargine-induced human bladder cancer T24 cell proliferation.

  6. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine.

    Arto Y Strandberg

    Full Text Available Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years.2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50 for detemir, and 0.55 (95% CI, 0.44-0.69 for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93 among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

  7. Body Composition and Epicardial Fat in Type 2 Diabetes Patients Following Insulin Detemir Versus Insulin Glargine Initiation.

    Elisha, B; Azar, M; Taleb, N; Bernard, S; Iacobellis, G; Rabasa-Lhoret, R

    2016-01-01

    The aim of the study was to compare body composition and epicardial fat thickness changes in insulin-naïve inadequately controlled patients with type 2 diabetes following basal insulin initiation with detemir vs. glargine. Six-month, open-label, interventional randomized pilot study was conducted. Dual-energy X-ray absorptiometry and echocardiography were used to estimate the body composition and epicardial fat thickness respectively. Thirty-six patients in the detemir group and 20 in the glargine group completed the study. Study groups baseline characteristics were comparable. At 6 months, for similar glycemic control, those on detemir significantly gained less total weight (0.6±2.5 vs. 4.2±4.1 kg, p=0.004), total fat mass (0.9±2.2 vs. 2.9±2.4 kg, p=0.02), and truncal fat mass (0.8±1.5 vs. 2.1±1.7 kg, p=0.02), with a loss in truncal lean mass (- 0.8±1.9 kg vs. 0.3±1.7 kg; p=0.02). EFT significantly decreased from baseline in both group (detemir - 1.7±0.52-mm, glargine - 1.1±1.6-mm; p<0.05, without significant difference inter-groups). Within the detemir group, epicardial fat thickness change correlated with truncal fat and total fat mass changes (r=0.65, p=0.06 and r=0.60, p=0.07). In conclusion, detemir resulted in less fat mass gain, a trend for a more pronounced epicardial fat thickness reduction when compared with glargine. PMID:26340704

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

    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. PMID:26470649

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

    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

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

    Ayşe Yasemin Çelik; Özgür Pirgon; Dursun Odabaş

    2010-01-01

    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 regul...

  11. Cost-utility of albiglutide versus insulin lispro, insulin glargine, and sitagliptin for the treatment of type 2 diabetes in the US.

    Bruhn, David; Martin, Alan A; Tavares, Ruben; Hunt, Barnaby; Pollock, Richard F

    2016-07-01

    Objective To compare the cost-utility of the glucagon-like peptide-1 receptor agonist albiglutide with those of insulin lispro (both in combination with insulin glargine), insulin glargine, and the dipeptidyl peptidase-4 inhibitor sitagliptin, representing treatments along the type 2 diabetes treatment continuum. Methods The Centre for Outcomes Research and Effectiveness (CORE) Diabetes Model was used for the cost-utility analysis. Data from three Phase 3 clinical trials (HARMONY 6, HARMONY 4, and HARMONY 3) evaluating albiglutide for the treatment of patients with type 2 diabetes were used for the baseline characteristics and treatment effects. Utilities and costs were derived from published sources. Results Albiglutide treatment was associated with an improvement in mean quality-adjusted life expectancy of 0.099, 0.033, and 0.101 years when compared with insulin lispro, insulin glargine, and sitagliptin, respectively. Over the 50-year time horizon, mean total costs in the albiglutide arm were $4332, $2597, and $2223 more than in the other respective treatments. These costs resulted in an incremental cost-utility ratio of $43,541, $79,166, and $22,094 per quality-adjusted life-year (QALY) gained for albiglutide vs insulin lispro, insulin glargine, and sitagliptin, respectively. At a willingness-to-pay threshold of $50,000 per QALY gained, there was a 53.0%, 41.5%, and 67.5% probability of albiglutide being cost-effective compared with the other respective treatments. Limitations This analysis was an extrapolation over a 50-year time horizon based on relatively short-term data obtained during clinical trials. It does not take into account potential differences between the respective treatments in adherence and persistence that can influence both effects and costs. Conclusions Albiglutide represents a reasonable treatment option for patients with type 2 diabetes based on its cost-utility, relative to insulin lispro, insulin glargine, and sitagliptin. PMID:26882484

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

    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.

  13. Concentrations of insulin glargine and its metabolites during long-term insulin therapy in type 2 diabetic patients and comparison of effects of insulin glargine, its metabolites, IGF-I, and human insulin on insulin and IGF-I receptor signaling

    A.J. Varewijck (Aimee); H. Yki-Jarvinen (Hannele); R. Schmidt (Reinhold); N. Tennagels (Norbert); J.A.M.J.L. Janssen (Joseph)

    2013-01-01

    textabstractWe investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during longterm insulin therapy in type 2 di

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

    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.

  15. Rationale, Design, and Baseline Data of the Insulin Glargine (Lantus) Versus Insulin Detemir (Levemir) Treat-To-Target (L2T3) Study: A Multinational, Randomized Noninferiority Trial of Basal Insulin Initiation in Type 2 Diabetes

    S.G.H.A. Swinnen; F.J. Snoek; M.P. Dain; J.H. DeVries; J.B.L. Hoekstra; F. Holleman

    2009-01-01

    Objective: To discuss the design and baseline data of the Lantus (R) (sanofi-aventis, Paris, France) versus Levemir (R) (Novo Nordisk A/S, Bagsvaerd, Denmark) Treat-To-Target (L2T3) study, a multinational, randomized comparison between the basal insulin analogs insulin glargine and insulin detemir.

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

    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

  17. Real-world outcomes of US employees with type 2 diabetes mellitus treated with insulin glargine or neutral protamine Hagedorn insulin: a comparative retrospective database study

    Wang, Li; Wei, Wenhui; Miao, Raymond; Xie, Lin; Baser, Onur

    2013-01-01

    Objectives To compare real-world outcomes of initiating insulin glargine (GLA) versus neutral protamine Hagedorn (NPH) insulin among employees with type 2 diabetes mellitus (T2DM) who had both employer-sponsored health insurance and short-tem-disability coverages. Design Retrospective cohort study. Setting MarketScan Commercial Claims and Encounters/Health and Productivity Management Databases 2003–2009. Participants Adult employees with T2DM who were previously treated with oral antidiabetic...

  18. Insulin

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  19. 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.

    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.

  20. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine

    Belhekar, Mahesh N; Sarayu Pai; Parimal Tayade; Pradip Dalwadi; Renuka Munshi; Prema Varthakavi

    2015-01-01

    Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutane...

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

    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

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

    Callesen, Nicoline F; Mathiesen, Jonathan Michael; Ringholm, Lene; Damm, Peter; Mathiesen, Elisabeth R

    2013-01-01

    Objective: To compare glycaemic control and pregnancy outcome in women with type 1 diabetes treated with the long-acting insulin analogues detemir or glargine. Methods: Retrospective study of singleton pregnancies from 2007 to 2011 in women with type 1 diabetes with a single living fetus at 22.......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....... 6.2% (4.8-7.2), p = 0.38). The incidence of severe hypoglycaemia was comparable (15 (23%) vs. 10 (23%), p = 0.98). Pre-eclampsia occurred in 9 (14%) vs. 8 (18%), p = 0.52, pre-term delivery in 21 (31%) vs. 16 (35%), (p = 0.70) and 33 (49%) vs. 14 (30%) infants were large for gestational age (p = 0...

  3. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial

    Bunck, M.C.M.; Diamant, M.; Corner, A.; Eliasson, B.; Malloy, J.L.; Shaginian, R.M.; Deng, W.; Kendall, D.M.; Taskinen, M.R.; Smith, U.; Yki-Jarvinen, H.; Heine, R.J.

    2009-01-01

    0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell

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

    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.

  5. Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus.

    Pfützner, Andreas; Stratmann, Bernd; Funke, Klaus; Pohlmeier, Harald; Rose, Ludger; Sieber, Jochen; Flacke, Frank; Tschoepe, Diethelm

    2016-09-01

    The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% (P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients. PMID:27325389

  6. Improving treatment satisfaction and other patient-reported outcomes in people with type 2 diabetes: the role of once-daily insulin glargine.

    Bradley, C; Gilbride, C J B

    2008-07-01

    Insulin therapy becomes essential for many people with type 2 diabetes. After starting insulin, people with diabetes that is poorly controlled with oral agents typically report improved well-being and treatment satisfaction. However, healthcare professionals and people with type 2 diabetes are often reluctant to begin insulin treatment, citing concerns such as time/resources needed to educate patients, increased risks of hypoglycaemia and fear of injections, which lead them to focus on intensifying conventional oral therapy. Insulin glargine, which offers people with diabetes a once-a-day injection regimen with low risk of hypoglycaemia, is more likely to overcome such initial barriers than other more complex insulin regimens. Once-daily insulin glargine, in combination with modern glucose-dependent oral agents that do not need to be chased with food to prevent hypoglycaemia, does not require the fixed mealtimes and set amounts of carbohydrates necessary with twice-daily injection mixes and older sulphonylureas. We know that it is such dietary restrictions that cause the most damage to quality of life (QoL). To avoid damaging QoL unnecessarily and to ensure optimal satisfaction with treatment, it is important to evaluate the effects of treatment on QoL, treatment satisfaction and other patient-reported outcomes (PROs) using questionnaires validated for this purpose, such as the widely used Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life measure. A systematic electronic literature search identified reports of studies evaluating PROs associated with insulin glargine in comparison with other treatments. The studies show that insulin glargine is usually associated with greater improvements in treatment satisfaction and other PROs compared with intensifying oral therapy or alternative insulin regimens. PMID:18577157

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

    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

  8. The cost-effectiveness of insulin glargine vs. neutral protamine Hagedorn insulin in type 2 diabetes: a focus on health economics.

    Levin, P

    2008-07-01

    Diabetes mellitus is a major public health problem, in particular because of long-term complications affecting essential organs, such as the eyes and kidneys, which can lead to a reduction in life expectancy and high healthcare costs. The number of individuals with diabetes mellitus is projected to rise worldwide from 171 million people in 2000 to 366 million people in 2030. With the number of patients with diabetes continually growing, the burden of pressure on worldwide health systems is huge. Accordingly, regulatory and marketing approvals of new medicines are beginning to incorporate economic evaluation techniques to determine their cost-effectiveness. Overall, the studies included in this review show that the initiation of insulin glargine is cost-effective and is expected to lead to substantial improvements in both life years (LYs) and quality-adjusted LYs compared with neutral protamine Hagedorn insulin. PMID:18577158

  9. Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: Results from a large population-based follow-up study

    Ruiter, Rikje; Visser, Loes; Coebergh, Jan Willem; Herk-Sukel, Myrthe; Haak, H.R.; Geelhoed-Duijvestijn, P.H.; Straus, Sabine; Herings, Ron; Stricker, Bruno

    2012-01-01

    Aims/hypothesis Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. Methods Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a...

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

    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. PMID:25239036

  11. Does a patient-managed insulin intensification strategy with insulin glargine and insulin glulisine provide similar glycemic control as a physician-managed strategy? Results of the START (Self-Titration With Apidra to Reach Target) Study: a randomized noninferiority trial.

    Harris, Stewart B; Yale, Jean-François; Berard, Lori; Stewart, John; Abbaszadeh, Babak; Webster-Bogaert, Susan; Gerstein, Hertzel C

    2014-01-01

    OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm. PMID:24170757

  12. Intensification of insulin therapy in patients with type 2 diabetes: a retrospective, non- interventional cohort study of patients treated with insulin glargine or biphasic human insulin in daily clinical practice

    2013-01-01

    Background The aim of this study is to compare the efficacy of intensification of insulin treatment with insulin glargine and biphasic human insulin in patients with type 2 diabetes on concomitant therapy with oral antidiabetic drugs (OAD) in daily clinical practice. Methods A retrospective multicentre parallel two-arm study included 301 patients with type 2 diabetes already on treatment with biphasic human insulin twice daily (bd) in combination with OAD. Data were collected retrospectively from 142 patients who had been switched from biphasic human insulin to insulin glargine in a period of 6–12 months prior to their inclusion (active group) and compared to data collected retrospectively from 159 patients who continued treatment with biphasic human insulin bd for the same time period (control group). Our primary objective was to examine the efficacy of the two treatments, assessed as change in HbA1c. Secondary objectives were to examine for changes in fasting blood glucose (FBG), body weight, treatment with OAD or fast-acting insulin and safety, by assessing the frequency and severity of hypoglycaemic episodes. Results At the end of the study there was a significant reduction in HbA1c in both arms. The least squares (LS) mean [(95% confidence intervals (CI)] reduction in HbA1c was -1.13 (-0.96 to -1.30)% in the active and -0.59 (-0.41to -0.77)% in the control group [LS mean treatment difference 0.53 (0.31-0.76)%, p < 0.001]. Similarly, fasting blood glucose declined significantly in both arms. The LS mean decline in FBG was -47.02 (-37.89 to -56.14) mg/dl in the active and -19.73 (-11.57 to -27.89) mg/dl in the control group [LS mean treatment difference 27.85 (15.74-39.95) mg/dl, p < 0.001]. No significant difference in hypoglycaemic episodes and in body weight was found. In the active group, more patients received rapid-acting pre-meal insulin and used insulin secretagogues drugs. Conclusions Glargine alone or in combination with fast acting insulin

  13. Concentrations of Insulin Glargine and Its Metabolites During Long-Term Insulin Therapy in Type 2 Diabetic Patients and Comparison of Effects of Insulin Glargine, Its Metabolites, IGF-I, and Human Insulin on Insulin and IGF-I Receptor Signaling

    Varewijck, Aimee J.; Yki-Järvinen, Hannele; Schmidt, Ronald; Tennagels, Norbert; Janssen, Joseph A.M.J.L.

    2013-01-01

    We investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m2, and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography–tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9–2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes. PMID:23569175

  14. 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

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

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic...... group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4.3 [SD 2.3] mmol/L vs -1.8 [2.3] mmol/L; p<0.0001) and nocturnal blood glucose (-3.3 [2.8] mmol/L vs -2.6 [2.9] mmol/L; p=0.0041) was better than it was in the insulin lispro group, whereas insulin...... lispro better controlled postprandial blood glucose throughout the day (p<0.0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5.2 [95% CI 1.9-8.9] vs 24.0 [21-28] events per patient per year; p<0.0001). Respective mean weight gains were 3.01 (SD 4.33) kg and 3...

  15. Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial.

    Heise, T; Bain, S C; Bracken, R M; Zijlstra, E; Nosek, L; Stender-Petersen, K; Rabøl, R; Rowe, E; Haahr, H L

    2016-02-01

    We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar. PMID:26450456

  16. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial

    Russell-Jones, D; Vaag, A; Schmitz, O;

    2009-01-01

    AIMS/HYPOTHESIS: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. METHODS: This randomised (using a telephone or web......-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1......Hg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and...

  17. COMPARISON OF INSULIN GLARGINE WITH HUMAN PREMIX IN SULIN IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTR OLLED ON ORAL HYPOGLYCEMIC DRUGS IN A 24-WEEK RANDOMIZED STUDY AMONG INDIAN POPULATION

    Abhishek

    2013-01-01

    Full Text Available ABSTRACT: INTRODUCTION: Type 2 diabetes is a progressive disorder of β-cell dysfunction. Patients using oral therapy alone for it seldom achi eve and maintain the recommended 7% HbA1c goal for glycemic control. However, the majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and use of insulin, which could improve glycemic control, is often long delayed and not agg ressive enough. Glargine, a long-acting insulin analog with a more favourable 24-h time-action profi le (no pronounced peak than long- or intermediate-acting human insulin preparations, may be especially suited in this condition. AIMS: To compare the safety and efficacy of the long-acti ng analog insulin glargine and human premix insulin in patients with type 2 diabetes who we re previously treated with oral hypoglycemic drugs alone but inadequately controlled . SETTINGS AND DESIGN: A total of 750 subjects with type 2 diabetes who were receiving or al hypoglycemic drugs for diabetes control were randomized to receive insulin glargine once da ily (n = 370 or human premix insulin twice daily (n = 380 for 24 weeks in an open-label, terti ary centre study. Doses were adjusted systematically to obtain target fasting glucose < 1 00mg/dl. Outcomes included fasting blood sugar, HbA1c levels, change in weight and insulin d ose from study start to end. STATISTICAL ANALYSIS: Qualitative variables were tested using Chi square test and p values were calculated between two groups. RESULTS: At the start of study, age range was 30-70 years, BMI was 26.48 +/- 6.3 kg/m (2 , and HbA1c was 11.9 +/-3.1%(mean +/- SD for both group. The mean change (means ± SD in HbA1c from baseline to end point was similar in the insulin glargine group (−3.0 ± 1.68% and the human premix insulin group (−2 .89 ± 1.79% (P value =0.3861. The symptomatic hypoglycemic episodes were greater with h uman premix insulin than with glargine (significance level 0.00002.Subjects in

  18. COMPARISON OF INSULIN GLARGINE WITH HUMAN PREMIX IN SULIN IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTR OLLED ON ORAL HYPOGLYCEMIC DRUGS IN A 24-WEEK RANDOMIZED STUDY AMONG INDIAN POPULATION

    Abhishek; Subodh; Dolly; Rajesh Kumar; Pragya

    2013-01-01

    ABSTRACT: INTRODUCTION: Type 2 diabetes is a progressive disorder of β-cell dysfunction. Patients using oral therapy alone for it seldom achi eve and maintain the recommended 7% HbA1c goal for glycemic control. However, the majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and use of insulin, which could improve glycemic control, is often long delayed and not agg ressive enough. Glargine, a long-acting insulin ...

  19. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    Pfohl, Martin; Siegmund, Thorsten; Pscherer, Stefan; Pegelow, Katrin; Seufert, Jochen

    2015-01-01

    Background Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice. Methods This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT). Results A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1). Conclusion Intensifying

  20. Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population.

    Barrio Castellanos, Raquel

    2005-12-01

    Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1. PMID:16398447

  1. 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.

    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.

  2. 格列美脲联合甘精胰岛素治疗2型糖尿病的疗效%Efficacy of glimepiride in combination with insulin glargine in treating type 2 diabetes

    公永明; 赵敏

    2011-01-01

    Objective; To observe the efficacy of glimepiride + insulin glargine in type 2 diabetes patients with secondary failure to sulfonylurea (SFS). Methods; Patients treated with glimepiride in combination with injection of insulin glargine (n =24) or Humulin 30R (n =30). The blood glucose, glycated hemoglobin (HbAlc) and serum C peptide were measured and compared at 12 weeks after treatment. Results; Both blood glucose and HbAlc were decreased (P<0.01 or <0. 05), and C peptide increased (P <0.05) after the two treatments. Conclusions; Treatment with glimepiride plus insulin glargine has satisfactory effect and may improve β cell function in patients with type 2 diabetes.%目的:观察磺脲类药物继发性失效者联合甘精胰岛素治疗2型糖尿病的疗效及胰岛β细胞功能变化.方法:对磺脲类药物继发性失效患者改用格列美脲,睡前分别注射甘精胰岛素(甘精组,24例)、优泌林30R(优泌林组,30例),12周后比较两组血糖、糖化血红蛋白(HbA1c)以及血清C肽的变化.结果:两组血糖和HbA1c均有下降(P<0.01或P<0.05),治疗后C肽升高(P<0.05).结论:联合甘精胰岛素治疗2型糖尿病有较好疗效,并有可能改善β细胞的功能.

  3. 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

    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

  4. Effect of Insulin Analogues on Insulin/IGF1 Hybrid Receptors: Increased Activation by Glargine but Not by Its Metabolites M1 and M2

    Cécile Pierre-Eugene; Patrick Pagesy; Tuyet Thu Nguyen; Marion Neuillé; Georg Tschank; Norbert Tennagels; Cornelia Hampe; Tarik Issad

    2012-01-01

    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 presenc...

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

    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

  6. The therapeutic effect of insulin glargine versu NPH insulin as add-on therapy to previous acarbose or metformin in senile obese type 2 diabetics%加用甘精胰岛素对老年肥胖2型糖尿病口服降糖药控制不佳患者的疗效

    王宾; 胡桂荣; 何丽; 孟红旗; 党静; 谢淑薏

    2012-01-01

    Objective To study the effectiveness and safety of insulin glargine versus isophane insulin as add-on therapy to previous OHA in senile obese type 2 diabetic patients who failed to control their blood glucose with oral hypoglycemic agents (OHA). Methods Sixty-one patients who failed to control their blood glucose with OHA were randomized into insulin glargine group and isophane insulin group. They were administered previous acarbose and/or metformin tablet and insulin glargine or isophand insulin as add-on therapy. The observation lasted for 12 weeks. Result (1) Both groups showed significant difference in HbAic FPG, and 2 hPG compared with before treatment, and in HbA1c and 2 hPG between the two groups (all P0. 05). (2) The BMI of the insulin glargine group was reduced by 2. 7 kg/m2 compared with before treatment) while that of the isophand insulin group was basically unchanged compared with before treatment (3) The 45. 2% of patients with insulin glargine treatment and the 73. 3% of patients with isophand insulin treatment had symptomatic hypoglycemia, and the difference was statistically significant (P<0. 05). (4) At the end of treatment, the dosa of insulin glargine group and isophand insulin group was (18. 7±3. 5) U/d and (26. 0±3. 7) U/d respectively, and the difference was statistically significant (P<0. 05). Conclusion The combination of insulin glargine with acarbose and/or metfonnin is effective in controlling the blood glucose, decreasing the incidence of hypoglycemia,and controlling the body weight of senile obese type 2 diabetic patients.%目的 研究口服降糖药控制不佳的老年肥胖T2DM患者加用甘精胰岛素或中效胰岛素联合应用治疗的有效性和安全性. 方法 将口服降糖药控制不佳的老年肥胖T2DM患者61例随机分为甘精胰岛素组和中效胰岛素组,治疗期内阿卡波糖和(或)二甲双胍剂量不变,分别加用甘精胰岛素或中效胰岛素每晚睡前注射1次联合治疗,进行12

  7. Clinical effect of insulin glargine and insulin aspart on poorly controlled patients with type 2 diabetes mellitus%甘精胰岛素联合门冬胰岛素对血糖控制不佳的2型糖尿病患者临床疗效分析

    邬培红

    2013-01-01

    目的 探讨甘精胰岛素联合门冬胰岛素治疗血糖控制不佳的2型糖尿病(T2DM)患者的临床疗效.方法 将86例T2DM患者随机分为2组,每组43例.观察组给予甘精胰岛素联合门冬胰岛素,对照组给予精蛋白生物合成人胰岛素联合生物合成人胰岛素.比较治疗3个月后2组空腹血糖(FPG)、餐后2h血糖(2 hPG)、糖化血红蛋白(HbAlc)水平的变化,以及血糖达标时间、体质量增加量、胰岛素日用量、血糖日波动量及低血糖发生率的差异.结果 观察组FPG、2hPG、HbAlc水平的改善幅度大于对照组;观察组血糖达标时间、体质量增加量、血糖日波动量及低血糖发生率均显著小于对照组.结论 对于血糖控制不佳的T2DM患者,甘精胰岛素与门冬胰岛素联合应用可理想控制血糖,减少体质量增加量,降低低血糖发生率,是安全而有效的胰岛素强化治疗方案.%Objective To explore the clinical effects of insulin glargine and insulin aspart on poorly controlled patients with type 2 diabetes mellitus (T2DM). Methods Eighty - six patients with T2DM were randomly divided into two groups, 43 cases in each group. The observation group received insulin glargine and insulin aspart, while the control group received biosynthetic human insulin and isophane protamine biosynthetic human insulin. After 3 - month treatment, the changes of fasting plasma glucose (FPG), plasma glucose 2 h after meals (2 hPG) and glycosylated hemoglobin (HbAlc) as well as the differences of target - hitting time of blood glucose, body mass increment, daily dosage of insulin, daily fluctuation quantity of insulin and hypoglycemic incidence in both groups were compared. Results The improved degrees of FPG, 2 hPG and HbAlc in the observation group were higher than that in the control group. The target - hitting time of blood glucose, body mass increment, daily dosage of insulin and hypoglycemic incidence in the observation group were

  8. One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension

    Riddle, M C; Yki-Järvinen, H; Bolli, G B; Ziemen, M; Muehlen-Bartmer, I; Cissokho, S; Home, P D

    2015-01-01

    Aims To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial. Methods EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed. Results Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c −0.17 [95% confidence interval (CI) −0.30 to −0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89–0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75–0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent. Conclusion During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between

  9. 加用甘精胰岛素或中效胰岛素的2型糖尿病患者血糖波动的比较%Comparison of the excursion of blood glucose in type 2 diabetes injected glargine and human isophane insulin

    曾龙驿; 穆攀伟; 张国超; 陈燕铭; 傅静奕; 王曼曼

    2009-01-01

    目的 比较空腹血糖控制不佳的2型糖尿病患者加用甘精胰岛素(glargine)或中效胰岛素治疗对血糖波动的影响.方法 30例口服抗糖尿病药治疗的2型糖尿病患者(空腹血糖>9.0 mmoL/L,HbA1C> 8.5%),按1:1随机分成两组,分别加用甘精胰岛素(来得时(R))或中效胰岛素(诺和灵(R)N)联合治疗.以空腹指尖毛细血管血糖0.05).结论 空腹血糖控制不佳的2型糖尿病患者加用甘精胰岛素比加用中效胰岛素治疗更有利于血糖的平稳,且不增加低血糖的风险.%Objective To compare the excursion of blood glucose (BG) in the type 2 diabetes mellitus treated with oral antidiabetic drugs (OADs) plus glargine or human isophane insulin (HII). Methods A 1 : 1 randomization schedule assigned 30 type 2 diabetics inadequately controlled on OADs (fasting BG>9.0 mmol/L and HbA1C > 8.5%) to 2 groups additionally treated with glargine or HII. The insulin dose was titrated to achieve fasting capillary BG<6.0 mmol/L. Montoring BG with continuous glucose monitoring system, then the standard deviation of BG (SDBG), maximal excursion of BG (LAGE) and coefficient of variation (CV) of fasting plasma glucose (FPG) were calculated. Results SDBG (1.49±0.35 vs 1.73±0.46), LAGE (3.23±0.76 vs 3.73± 1.00) and CV-FPG (17.26±2.24 vs 20.33±3.21) were lower in glargine group than those in HII group (P< 0.05). No difference could be found in hypoglycaemia between two groups. Conclusion OADs plus glargine could make blood glucose more stable than OADs plus HII without increasing the incidence of hypoglycaemia.

  10. Clinical Observation of Therapeutic Efficiency of Insulin Glargine Combined with Oral Hypoglycemic Agents in Elderly Patients with Type 2 Diabetes%甘精胰岛素联合口服降糖药治疗2型糖尿病临床观察

    何启胜

    2011-01-01

    目的 观察甘精胰岛素联合口服降糖药物治疗2型糖尿病的临床疗效和安全性.方法 选择口服降糖药物血糖控制不佳的56例老年2型糖尿病患者,随机分为加用甘精胰岛素治疗组和低精蛋白锌胰岛素组两组,观察治疗前和治疗24周后各组的FBG、P2hBG、HbA1c和BMI的变化.同时对两种方案的安全性进行比较.结果 治疗24周后甘精胰岛素组与低精蛋白锌胰岛素组均能降低FBG、P2hBG、HbAlc,且疗效相当,组内治疗前后比较差异无统计学意义,而BMI均没有明显变化.但甘精胰岛素组的严重低血糖发生率明显低于低精蛋白锌胰岛素组.结论 甘精胰岛素组与低精蛋白锌胰岛素组在降低血糖方面的疗效相当,但甘精胰岛素组比低精蛋白锌胰岛素组治疗安全性高.%Objective To evaluate the clinical observation of therapeutic efficiency and safty of insulin glargine combined with oral hypoglycemic agents in elderly patients with type 2 diabetes. Methods Fifty six elderly patients with type 2 diabetes and poorly glycemic control by oral medication were randomly divided into two groups: insulin glargine( + ) group and isophane insu-lin( + ) group. FBG,P2hBG,HbAlc and BMI in each group were measured before and after 24 weeks of treatment,and the adverse effect were also recorded. Results HbAlc,FBG and P2hBG of the two groups were declined obviously after 24 weeks of treatment,and the therapeutic equivalence between the two groups. No significant change of BMI in the two groups. But the incidence of severe hypoglycemia in the insulin glargine group was lower than that in the isophane insulin group. Conclusion The therapeutic equivalence of insulin glargine and isophane insulin in decreasing the blood sugar was observed,but the security in insulin glargine group was higher than that in the low protamine zinc insulin group.

  11. Concentrated insulins: the new basal insulins

    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. Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

    Bo F Hansen; Glendorf, Tine; Hegelund, Anne C.; Lundby, Anders; Lützen, Anne; Slaaby, Rita; Stidsen, Carsten Enggaard

    2012-01-01

    Aims/Hypothesis There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. Methods We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. Results Detemir and glargine each ...

  13. Insulin Glargine (rDNA origin) Injection

    ... cloudy, or contains solid particles, or if the expiration date on the bottle has passed.Do not ... body wheezing difficulty breathing or swallowing shortness of breath fast pulse sweating swelling of the eyes, face, ...

  14. Clinical Research on Elderly Patients with Type 2 Diabetes Complicated by Medical Critical Illness Treated by Insulin Glargine%甘精胰岛素治疗老年2型糖尿病合并内科危重患者的临床研究

    王晓飞

    2014-01-01

    Objective To investigate and analyze the clinical effect of insulin glargine on elderly patients with type 2 diabetes complicated by medical critical illness. Methods For patients in the control group, human insulin isophane was given to them and short-acting insulin was also given to the patients who were able to eat before meals for controlling the blood glucose concentration within the range of 5.0~8.0 mmol/L. And insulin glargine was given to the patients in the experimental group on the basis of the treatment given to the control group. Results The average blood glucose concentration of the experimental group and the control group 1, 3, 5d after treatment was (12.1±5.1) mmol/L, (7.6±1.2) mmol/L, (5.5±0.9) mmol/L;(13.4±5.7) mmol/L, (10.8±2.0) mmol/L, (6.6 ±1.0) mmol/L, respectively. Conclusion For elderly patients with type 2 diabetes complicated by medical critical illness in clinical practice, insulin glargine can effectively control the blood glucose level, alleviate the pain, improve the treatment effect, promote the rehabilitation of the patients and enhance the quality of life of the patients.%目的:探讨对老年2型糖尿病合并内科危重疾病患者采用甘精胰岛素治疗,探讨和分析其治疗的临床效果。方法选取该院2011年1月—2013年7月期间收治的110例老年2型糖尿病合并内科危重疾病患者。对照组:对患者采用中性低精蛋白锌人胰岛素进行治疗,可进食的患者,餐前给患者追加短效胰岛素,将患者的血糖浓度控制在5.0~8.0 mmol/L 范围内;试验组:在对照组治疗基础上,对患者采用甘精胰岛素治疗。结果经过治疗后,试验组和对照组在1、3、5d的平均血糖浓度分别为(12.1±5.1)mmol/L、(7.6±1.2)mmol/L、(5.5±0.9)mmol/L;(13.4±5.7)mmol/L、(10.8±2.0)mmol/L、(6.6±1.0)mmol/L;结论在临床上,对老年2型糖尿病合并内科危重疾病患者采用甘精胰岛素进行治疗,有效地控制患者的

  15. 甘精胰岛素与格列本脲治疗初诊2型糖尿病的疗效对比%Comparison on the clinical effects of insulin glargine and glimepiride for newly diagnosed type 2 diabetes mellitus

    班安然

    2013-01-01

    Objective To compare the therapeutic effects and safety of insulin glargine and glimepiride in the treatment of newly diagnosed type 2 diabetes mellitus (T2DM). Methods Sixty T2DM patients were randomly divided into 3 groups, 20 cases in each group. Group A was administered insulin glargine combined with metformin, group B glimepiride combined with metformin and group C Isophane Protamine Biosynthetic Human Insulin Injection (pre - mix 30R). Before and after treatment, the levels of fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2 hPG), glycosylated hemoglobin (HbAlc) and postprandial C peptide after meals in the patients of 3 groups as well as hypoglycemia incidences of groups A and B were compared. Results The improved condition of each index in group A was markedly superior to those in groups B and C. The improved conditions of group B showed the tendency of preceding group C, but there was no statistical significance among each indexes except for HbAlc. The hypoglycemia incidences of group A in both previous and later 6 weeks showed the tendency of being inferior to group B, but the difference showed no statistical significance. Conclusion Insulin glargine combined with metformin in the treatment of T2DM, can significantly reduce the blood sugar and ameliorate glycometabolism, with a low incidence of hypoglycemia, high safety and superior to glimepiride combined with metformin, so it is worthy of clinical promotion.%目的 比较甘精胰岛素与格列本脲对初诊2型糖尿病(T2DM)的疗效及安全性.方法 将60例T2DM患者随机分为3组,每组20例.A组给予甘精胰岛素联合二甲双胍,B组给予格列本脲联合二甲双胍,C组给予精蛋白生物合成人胰岛素注射液(预混30R).比较3组患者治疗前后空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbAlc)、餐后C肽水平变化,以及A、B组低血糖发生率.结果 A组各指标改善情况均显著优于B、C组,B组各指标改善情况有

  16. 甘精胰岛素佐治老年2型糖尿病肾病的临床价值分析%Clinical value analysis of insulin glargine treatment for elderly patients with type 2 diabetes complicated with nephropathy

    李晓红

    2013-01-01

    Objective To investigate the clinical value of insulin glargine treatment for elderly patients with type 2 diabetes complicated with nephropathy. Methods 80 cases of elderly patients with type 2 diabetes complicated with nephropathy admitted to our hospital from May 2010 to May 2011 were randomly divided into two groups, control group( n =40 )and treatment group( n =40 ). The control group was given isophane protamine biosynthetic human insulin and repaglinide, the treatment group was given insulin glargine and repaglinide. The clinical efficacy, blood glucose and renal function of the two groups were observed and compared. Results The total effective rate of treatment group was significantly higher than that of control group( 92. 50% vs. 75. 00% , P < 0. 05 ); the incidence of hypoglycemia/ nocturnal hypoglycemia of treatment group was significantly lower than that of control group( P < 0. 05 ); the level of fasting plasma glucose,2-hour postprandial plasma glucose,glycated hemoglobin Alc of the treatment group after treatment were significantly less than those of control group( P < 0. 05 ); the level of blood urea nitrogen, serum creatinine, 24-hour urine protein of treatment group after treatment were significantly improved than those of control group( P < 0. 05 ). Conclusion The clinical application of insulin glargine for the elderly patients with type 2 diabetic nephropathy can significantly control the blood glucose and improve the patient's renal function.%目的 探讨甘精胰岛素佐治老年2型糖尿病肾病的临床价值.方法 将2010年5月至2011年5月我院诊治的80例糖尿病肾病患者随机分成2组:对照组40例,采用精蛋白生物合成人胰岛素+瑞格列奈治疗;试验组40例,采用甘精胰岛素+瑞格列奈治疗.观察比较两组的临床疗效、血糖水平和肾功能水平的变化情况.结果 试验组的总有效率显著高于对照组(92.50% vs.75.00%,P<0.05),试验组的低血糖/夜间低血糖的不良反

  17. 甘精胰岛素和人胰岛素对人乳腺癌MDA-MB-231细胞的增殖作用%Effect of insulin glargine and human insulin on proliferation f a human breast cancer cell line MDA-MB-231

    刘珊英; 李焱; 潘秋辉; 魏菁; 梁颖; 傅玉如; 梁蔚文; 林天歆

    2010-01-01

    目的 探讨甘精胰岛素(insulin glargine)和人胰岛素(human insulin)对人乳腺癌细胞株MDA-MB-231增殖的影响及细胞外信号调节激酶(ERK)的调节作用.方法 使用不同浓度的甘精胰岛素和人胰岛素刺激人乳腺癌MDA-MB-231细胞株,检测不同时间段的细胞增殖作用,探讨抑制ERK1/2激活对细胞增殖的影响.使用cell counting kit-8(CCK-8)试剂检测细胞增殖,流式细胞术检测细胞周期分布.结果 甘精胰岛素和人胰岛素在1、10、100 IU·L-1刺激MDA-MB-231细胞96 h后均可轻度促进MDA-MB-231细胞增殖,相同条件下甘精胰岛素和人胰岛素的促增殖效应无差异.甘精胰岛素与人胰岛素以10 IU·L-1分别刺激48、72、96 h后两药均诱导细胞增殖,比较两种药物间增殖效应的差异无统计学意义.甘精胰岛素和人胰岛素均使S+G2/M期细胞比例增加,但两处理组间差异无显著性.ERK1/2抑制剂PD98059可抑制MDA-MB-231细胞增殖;但PD98059不影响甘精胰岛素和人胰岛素对MDA-MB-231细胞增殖的促进作用.结论 甘精胰岛素和人胰岛素对人乳腺癌细胞株MDA-MB-231增殖有类似的轻度促进作用,该作用不依赖于ERK的激活.

  18. Clinical Observation of 105 Cases with Insulin Glargine Plus Oral Hypoglycemic Drugs for Treating Type 2 Diabetes%甘精胰岛素加口服降糖药治疗2型糖尿病105例临床观察

    刘红丽; 王叶菊

    2011-01-01

    Objective To observe the therapeutic efficacy and safety of insulin glargine plus acarbose on patients with type 2 diabetes with poor efficacy of premixed human insulin in converted. Methods To se-lect105 patients with type 2 diabetic in Hanzhong Central Hospital from 2008 June to 2010 June inpatient, previous use of premixed human insulin 30R, poor glycemic control or hypoglycemia has emerged frequently, conversion of insulin glargine plus acarbose treatment. After 12 weeks,fasting blood glucose( FBG ),2-hour plasma glucose( 2hPG ),hemoglobin A1C( HbAlC )and recorded the incidence rate of hypoglycemia, changes in body mass and insulin dose were observed. Results In98 cases,fasting blood glucose,2-hour plasma glucose, hemoglobin A1C compliance rate was respectively 92% ,87% ,83% ,the incidence of hypoglycemia significantly decreased, insulin dose was reduced, the body mass was not significant changes. Conclusion For patients with poor effect of premixed human insulin in treatment of poor patients," 2 back 1" treatment strategy to provide better glycemic control, and reduce the rate of hypoglycemia.%目的 观察预混人胰岛素疗效不佳的2型糖尿病患者转换甘精胰岛素加阿卡波糖治疗后的疗效及安全性.方法 选取汉中市中心医院2008年6月至2010年6月住院的2型糖尿病患者105例,既往使用预混人胰岛素30R,血糖控制不佳或频繁出现低血糖者,转换甘精胰岛素加阿卡波糖治疗.12周后观察空腹血糖、餐后2 h血糖、糖化血红蛋白,并记录低血糖发生次数、体质量变化及胰岛素剂量.结果 98例患者空腹、餐后2 h血糖、糖化血红蛋白达标率分别是92%、87%、83%,低血糖发生率明显降低,胰岛素剂量较前减少,体质量无明显变化.结论 对于预混人胰岛素治疗欠佳的患者,"2退1"的治疗策略能提供更佳的血糖控制,并减少低血糖的发生率.

  19. The Effect of Basal Analog Insulin on the Glycemic Variability in Type 2 Diabetics

    Soner Cander

    2014-06-01

    Full Text Available Purpose: The aim of this study was to investigate the effect of insulin detemir and glargine on glycemic variability as determined by capillary blood glucose measurements in Type 2 diabetics treated with oral antidiabetic drugs. Material and Method: A total of 64 insulin-naive type 2 diabetics with a HbA1c level of 7.5%-10% were included in the study. The patients were randomized into 3 groups according to the basal insulin analog started; Group 1 (n=22 was started on once-daily detemir, Group 2 (n=22 twice-daily detemir, and Group 3 (n=20 insulin glargine. Basal insulin doses were titrated according to the morning/evening fasting capillary blood glucose levels. Standard deviations of the 8-point intraday fasting and postprandial blood glucose values were compared. Results: The fasting blood glucose intraday standard deviation values showed an improvement of 22.4% in Group 1, 21.4% in Group 2, and 26.4% in Group 3, while the intraday standard deviation for the postprandial values showed an improvement of 14.4%, 15.2%, and 38.7%, respectively (p>0.05. The standard deviation values did not show statistical significance when the groups were compared with each other. Baseline HbA1c values and insulin doses negatively correlated with the glycemic variability. Dicussion: Basal insulin added to treatment in Type 2 diabetics provided an improvement of 14.4% to 38.7% in glycemic variability. There was no significant difference between insulin glargine and detemir regarding this effect. Turk Jem 2014; 2: 33-38

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

    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.

  1. 老年2型糖尿病内科危重患者应用甘精胰岛素治疗的临床分析%Clinical Analysis the Severe Patients With Agedness Type 2 Diabetes Application for Insulin Glargine in Medicine

    邢丽英; 姜丽萍

    2015-01-01

    Objective To explore the application in elderly patients with type 2 diabetes mellitus and medical critically ill the clinical effect of insulin therapy.Methods Selected 98 cases of elderly patients with type 2 diabetes mellitus and medical critically ill in our hospital as the object, were randomly divided into the control group and the treatment group, each group had 49 cases.The control group received neutral isophane human insulin therapy, the treatment group on the basis of received insulin glargine in the control group, compared clinical effect of two groups. Results The treatment group at 1 days, section 3 days, 5 days average blood glucose concentration was less than that in the control group,P<0.05, was difference had statistically significance. the treatment a few days rest and treatment comparison average blood glucose concentration after 7 dsys,P>0.05, was no difference had statistically significance.Conclusion Elderly patients with type 2 diabetes mellitus and internal critical application of insulin treatment, can well control blood sugar levels and improve the treatment effect.%目的 探讨老年2型糖尿病内科危重患者应用甘精胰岛素治疗的临床效果.方法 将我院收治的98例老年2型糖尿病合并内科危重患者作为研究对象,随机分为对照组与治疗组,各49例,对照组给予中性低精蛋白锌人胰岛素治疗,治疗组在对照组基础上应用甘精胰岛素治疗,对比两组患者的临床效果.结果 治疗组在第1 d、第3 d、第5 d的平均血糖浓度要少于对照组,P<0.05,差异具有统计学意义;其余治疗天数与治疗7 d后平均血糖浓度对比,P>0.05,差异不具有统计学意义.结论 老年2型糖尿病合并内科危重患者应用甘精胰岛素治疗,能够较好地控制血糖水平,改善治疗效果.

  2. 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

    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

  3. 甘精胰岛素治疗2型糖尿病合并慢性肾脏疾病患者的临床观察%Clinical Observation of Patients with Type 2 Diabetes and Chronic Kidney Disease Treated by Insulin Glargine

    彭耀尧

    2014-01-01

    目的:探讨对2型糖尿病合并慢性肾脏疾病患者采用甘精胰岛素治疗,探讨和分析其治疗的临床效果。方法将该院2012年10月—2013年12月期间所收治的55例2型糖尿病合并慢性肾脏疾病患者,按照随机数字表法分组为观察组(30例)和对照组(25例);治疗前,观察组和对照组患者24 h内的血糖平均浓度分别为(13.7±5.7)mmol/L、(13.4±6.0)mmol/L;对照组:采用中性低精蛋白锌人胰岛素进行治疗,可进食的患者,餐前追加短效胰岛素,将血糖浓度控制在5.0~8.0 mmol/L范围内;观察组:在对照组治疗基础上采用甘精胰岛素治疗。结果经过治疗后,观察组和对照组在1、3、5d的平均血糖浓度分别为(11.9±4.8)mmol/L、(7.4±1.3)mmol/L、(5.6±0.7)mmol/L;(13.5±5.6)mmol/L、(10.7±1.9)mmol/L、(6.5±0.8)mmol/L(P0.05)。结论在临床上,对2型糖尿病合并慢性肾脏疾病患者采用甘精胰岛素进行治疗,有效地控制患者的血糖水平,减轻患者痛苦,改善其临床症状,提高患者生活质量。%Objective To study and analyze the clinical effect of insulin glargine in the treatment of type 2 diabetes complicated by chronic kidney disease. Methods 55 patients with type 2 diabetes complicated by chronic kidney disease admitted in our hos-pital were grouped into the observation group (30 cases) and control group (25 cases) according to the random number table. Before treatment, the average blood glucose concentration within 24h of the observation group and the control group was(13.7±5.7)mmol/L, (13.4 ±6.0)mmol/L, respectively. For patients in the control group, human insulin isophane was given to them for treatment, and short-acting insulin was also given to the patients who were able to eat before meals for controlling the blood glucose concentration within the range of 5.0~8.0 mmol/L. And for patients in the observation group, insulin glargine was given to them on the basis of the

  4. Insulin analogs and cancer

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

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

    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...

  6. Clinical curative effect and safety analysis of insulin glargine and acarbose treatment in elderly diabetes patients%甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性评价

    王筱景; 阮凌燕; 周小爱

    2014-01-01

    目的:评价甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性。方法老年糖尿病患者120例随机分为治疗组和对照组,各60例。治疗组用甘精胰岛素联合阿卡波糖,对照组用精蛋白生物合成人胰岛素注射液联合阿卡波糖,胰岛素始剂量为0.15 U・ kg-1,根据血糖水平调整胰岛素用量及口服药物用量,随访观察3个月。监测患者血糖水平,并记录不良事件;随访记录2组患者的血糖达标时间和每日胰岛素总量,计算日平均血糖,检测患者治疗后的糖化血红蛋白水平和空腹 C 肽值。结果治疗3个月后,患者的糖化血红蛋白、空腹血糖及日平均血糖水平较治疗前均降低(P <0.05),其中,治疗组的日平均血糖水平显著低于对照组(P <0.05)。治疗组的血糖达标时间和胰岛素日用量均少于对照组(P 均<0.05),治疗后空腹 C 肽含量明显高于对照组(P <0.05)。治疗组的不良反应发生率低于对照组(P <0.05)。结论甘精胰岛素联用阿卡波糖治疗老年糖尿病患者具有良好疗效,能快速、安全、有效地控制患者血糖。%Objective To study the clinical curative effect and safety analysis of insulin glargine with acarbose treatment in elderly patients with diabetes.Methods A total of 120 cases of elderly patients with diabetes were randomly divided into two groups.The 60 patients of treat-ment group were treated with insulin glargine and acarbose combination , and the 60 patients of the control group were treated with isophane prota -mine biosynthetic human insulin injection and acarbose combination .The patient monitored blood glucose levels and recorded adverse events .The therapeutic time and the daily amount of insulin were recorded of two groups of patients.The average daily blood sugar were calculated and the HbA1c and fasting c -peptide values were detected at 3 months

  7. Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin

    Ahmann, Andrew

    2015-01-01

    Type 2 diabetes mellitus (T2DM) management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2) inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates ...

  8. Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis

    Umpierrez, Guillermo E.; Jones, Sidney; Smiley, Dawn; Mulligan, Patrick; Keyler, Trevor; Temponi, Angel; Semakula, Crispin; Umpierrez, Denise; Peng, Limin; Cerón, Miguel; Robalino, Gonzalo

    2009-01-01

    OBJECTIVE To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34). RESULTS There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03). CONCLUSIONS Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA. PMID:19366972

  9. Treatment with insulin (analogues) and breast cancer risk in diabetics

    Bronsveld, Heleen K; Ter Braak, Bas; Karlstad, Øystein;

    2015-01-01

    animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However, the...

  10. Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

    Karlstad, Oystein; Starup-Linde, Jacob; Vestergaard, Peter;

    2013-01-01

    . Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin......BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case......-control studies examining risk of cancer associated with insulin use in patients with diabetes. DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS): POPULATION: diabetes patients. EXPOSURE: Users of any...

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

    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.

  12. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  13. Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's Disease (sAD)-Like Pathology.

    Kamat, Pradip K; Kalani, Anuradha; Rai, Shivika; Tota, Santosh Kumar; Kumar, Ashok; Ahmad, Abdullah S

    2016-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology. PMID:26298663

  14. Functional Evaluation of the Reusable JuniorSTAR® Half-Unit Insulin Pen

    Klonoff, David; Nayberg, Irina; Rabbone, Ivana; Domenger, Catherine; Stauder, Udo; Oualali, Hamid; Danne, Thomas

    2015-01-01

    Background: The functional performance of the JuniorSTAR® (Sanofi, Paris, France) half-unit insulin pen was evaluated through a series of specific objective tests to assess the dose accuracy, pen weight, injection force, and dialing torque. Method: Pens (n = 60) were tested under standard atmospheric conditions with 3 different types of insulins manufactured by Sanofi (insulin glargine, insulin glulisine, and biphasic insulin isophane). The dose accuracy was tested according to the ISO 11608-...

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

    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.

  16. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  17. Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

    Hansen, Bo F.; Glendorf, Tine; Hegelund, Anne C.; Lundby, Anders; Lützen, Anne; Slaaby, Rita; Stidsen, Carsten Enggaard

    2012-01-01

    Aims/Hypothesis There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. Methods We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. Results Detemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. Conclusions Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir. PMID:22590494

  18. Molecular characterisation of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10.

    Bo F Hansen

    Full Text Available AIMS/HYPOTHESIS: There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. METHODS: We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. RESULTS: Detemir and glargine each displayed a balanced affinity for insulin receptor (IR isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤ 1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. CONCLUSIONS: Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir.

  19. Basal insulin analogues in the management of diabetes mellitus: What progress have we made?

    Owens, David R; Matfin, Glenn; Monnier, Louis

    2014-02-01

    Insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been the predominant basal insulin in clinical use. However, absorption is variable due to the need for resuspension and the time-action profile (peak activity 4-6 h after subcutaneous administration) confers an increased propensity for between-meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology enabled modifications to the insulin molecule resulting in the soluble long-acting insulin analogues, glargine and detemir. Both exhibit a lower risk of hypoglycaemia compared with neutral protamine Hagedorn due to improved time-action profiles and reduced day-to-day glucose variability. Glargine is indicated for administration once daily and detemir once or twice daily. Degludec is the latest prolonged-acting insulin which forms long subcutaneous multi-hexamers that delay absorption. Recent phase III trials in type 1 and type 2 diabetes show that degludec was non-inferior to comparators (predominantly glargine) with a minimal although inconsistent reduction in overall hypoglycaemia and a small absolute difference in nocturnal hypoglycaemia. Newer developmental agents include LY2605541 and glargine U300. LY2605541 comprises insulin lispro combined with polyethylene glycol, thereby increasing its hydrodynamic size and retarding absorption from the subcutaneous tissue. Glargine U300 is a new formulation of glargine resulting in a flatter and more prolonged time-action profile than its predecessor. This article reviews recent advances in basal insulin analogues, including a critical appraisal of the degludec trials. PMID:24026961

  20. Drug: D03250 [KEGG MEDICUS

    Full Text Available D03250 Drug Insulin glargine (genetical recombination) (JAN); Insulin glargine (USA...llaneous 2492 Pancreatic hormones D03250 Insulin glargine (genetical recombinatio...ogues for injection, long-acting A10AE04 Insulin glargine D03250 Insulin glargine (genetical recombination) ...cose Regulators Insulins Insulin glargine D03250 Insulin glargine (genetical recombination) (JAN); Insulin g...7] Insulin glargine [ATC:A10AE04] D03250 Insulin glargine (genetical recombination) (JAN); Insulin glargine

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

    Raslova, Katarina

    2010-01-01

    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. PMID:20539842

  2. Cardiovascular effects of basal insulins

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  3. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†

    Haukka, Jari; Hoti, Fabian; Erästö, Panu; Saukkonen, Tero; Mäkimattila, Sari; Korhonen, Pasi

    2013-01-01

    Objective Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from ...

  4. Human Insulin Does Not Increase Bladder Cancer Risk

    Chin-Hsiao Tseng

    2014-01-01

    BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the ent...

  5. 甘精胰岛素联合阿卡波糖与预混胰岛素治疗2型糖尿病的效果比较%Study on the effects of glargined with acarbose and isophane protamine biosynthetcic human insulin in patients with type 2 diabetic

    李艳萍; 李红梅

    2009-01-01

    目的 比较甘精胰岛素(Glargine)联合阿卡波糖与预混胰岛素(精蛋白生物合成人胰岛素30R)治疗2型糖尿病的疗效及对血糖波动的影响.方法 将65例2型糖尿病随机分为A组采用甘精胰岛素联合阿卡波糖治疗,B组采用预混胰岛素每日2次皮下注射.以空腹血糖(mFBG)<7mmol/L为目标,并监测早餐后2h血糖(mFPIG),午餐后2h血糖(mFP2G)和晚餐后2h血糖(mFP3G)计算1d 4次血糖样本的标准差(SD),以及最高和最低血糖之差(△).观察两组的血糖波动、胰岛素日用量、低血糖发生率.结果 A组胰岛素日用量、低血糖发生率均低于B组(P<0.05),血糖波动小.结论 甘精胰岛素联合阿卡波糖治疗2型糖尿病比预混胰岛素更利于血糖的平稳,低血糖的发生率低,波动影响更小,患者依从性好.

  6. Starting Insulin in Type 2 Diabetes: Real-World Outcomes After the First 12 Months of Insulin Therapy in a New Zealand Cohort

    Sehgal, Shekhar; Khanolkar, Manish

    2015-01-01

    Aims Currently, there is no consensus on which form of insulin to use when initiating insulin in type 2 diabetes (T2D). Our aim was to compare glycated hemoglobin (HbA1C) reduction, weight change and severe hypoglycemia rates during the first year after initiation of intermediate-acting insulin isophane, insulin glargine and pre-mixed insulin in patients with T2D. Methods Electronic clinical records of patients with T2D, starting insulin at a tertiary referral center in Auckland, New Zealand,...

  7. Cardiovascular effects of basal insulins.

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  8. Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin?

    Kulozik, Felix

    2013-01-01

    Objectives: In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction. Methods: The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft–Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters. Results: The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR. Conclusions: Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is

  9. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†

    Haukka, Jari; Hoti, Fabian; Erästö, Panu; Saukkonen, Tero; Mäkimattila, Sari; Korhonen, Pasi

    2013-01-01

    Objective Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables. Results The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6–32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5–17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9–55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI −10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2–42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1–25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine. Conclusions There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice. PMID:24150837

  10. The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS)

    Cassani, Roberta Soares Lara; Forti, Adriana Costa e; Pareja, José Carlos; Tambascia, Marcos Antonio; Geloneze, Bruno

    2016-01-01

    Background The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. Objectives To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. Subjects/Methods The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18–65 years old, BMI: 18.5–49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria. Results For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. Conclusions The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities. PMID:27490249

  11. Insulin degludec. Uncertainty over cardiovascular harms.

    2014-06-01

    Insulin isophane (NPH) is the standard long-acting human insulin for patients with type 1 and type 2 diabetes. Long-acting human insulin analogues are also available: insulin glargine and insulin detemir. Uncertainties remain concerning their long-term adverse effects. Insulin degludec (Tresiba, Novo Nordisk) is another long-acting human insulin analogue, also approved in the EU for patients with type 1 and type 2 diabetes. It was authorised at a concentration of 100 units per ml, like other insulins, and also at a concentration of 200 units per ml. There are no comparative data on insulin degludec 200 units per ml in patients using high doses of insulin. Insulin degludec has mainly been evaluated in ten randomised, unblinded, "non-inferiority" trials lasting 26 to 52 weeks, nine versus insulin glargine and one versus insulin detemir. Insulin degludec was administered at a fixed time each evening, or in either the morning or evening on alternate days, at varying intervals of 8 to 40 hours between doses. Efficacy in terms of HbA1c control was similar to that of the other insulin analogues administered once a day. The frequency of severe hypoglycaemia was similar in the groups treated with insulin degludec and those treated with the other insulins (10% to 12% among patients with type 1 diabetes and less than 5% in patients with type 2 diabetes). Deaths and other serious adverse events were similarly frequent in the different groups. A meta-analysis of clinical trials, carried out by the US Food and Drug Administration, suggested an increase of about 60% in the incidence of cardiovascular complications, based on a composite endpoint combining myocardial infarction, stroke and cardiovascular death. Other adverse effects observed in these trials were already known to occur with human insulin and its analogues, including weight gain, hypersensitivity reactions, reactions at the injection site, etc. The trials were too short in duration to assess long-term harms

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

    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

  13. Safety of pramlintide added to mealtime insulin in patients with type 1 or type 2 diabetes: a large observational study.

    Pencek, R; Roddy, T; Peters, Y; De Young, M B; Herrmann, K; Meller, L; Nguyen, H; Chen, S; Lutz, K

    2010-06-01

    The objective of this Phase 4, open-label, multicentre, observational study was to fulfil food and drug administration (FDA) postapproval requirement to evaluate in healthcare practices the risk of insulin-induced severe hypoglycaemia following initiation of pramlintide therapy in N = 1297 patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) with inadequate glycaemic control. The duration of the study was approximately 6 months. During the adjustment period (0-3 months), the incidence and event rate of patient-ascertained severe hypoglycaemia (PASH) were 4.8% and 0.33 events/patient-year in patients with T1DM and 2.8% and 0.19 events/patient-year in patients with T2DM. During the maintenance period (>3-6 months), the incidence and event rate of PASH declined in patients with T1DM or T2DM. This study confirms that in healthcare practices, the risk of insulin-induced severe hypoglycaemia following the initiation of pramlintide is low in patients with T1DM or T2DM. PMID:20518811

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

    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.

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

    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. PMID:21714872

  16. Cancer specific mortality in insulin-treated type 2 diabetes patients.

    Sorin Ioacara

    Full Text Available AIMS: To test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients. METHODS: All consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869. Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥ 80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin. RESULTS: Mean baseline age was 62 ± 9 years, and follow-up 4.7 ± 1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89-0.99, p = 0.033. Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89-0.99, p = 0.018 and cumulative dose of glargine (0.92 (95%CI 0.86-0.98, p = 0.014. Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins. CONCLUSIONS: The cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional "fixed" cohort or propensity score analyses.

  17. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec.

    Robinson, Jennifer D; Neumiller, Joshua J; Campbell, R Keith

    2012-12-24

    The basal-bolus concept of delivering insulin to diabetic patients makes physiological sense, as it mimics normal insulin release in people without diabetes. In line with this concept, a major effort put forth by insulin manufacturers has been to develop the ideal exogenous basal insulin product. The perfect basal insulin product would be injected into subcutaneous tissue without causing irritation, release insulin continuously at a constant rate for at least 24 hours, be stable, not contribute to weight gain, have a low risk of allergic reactions and, very importantly, minimize the risk of hypoglycaemia. While the perfect insulin has not yet been discovered, advancements are still being made. Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Insulin degludec achieves these pharmacokinetic properties by forming soluble multihexamers upon subcutaneous injection, resulting in the formation of a depot in the subcutaneous tissue that is slowly released and absorbed into circulation. Insulin degludec has been associated with slightly less weight gain and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in some, but not all, clinical studies. This article briefly reviews current evidence for the use of insulin degludec in patients with type 1 or type 2 diabetes mellitus and discusses the potential impact of this new basal insulin on clinical practice. PMID:23145524

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

    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

  19. Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus.

    Yki-Järvinen, Hannele

    2002-01-01

    The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes. PMID:12324990

  20. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes-a protocol for a randomised, double-blind, placebo-controlled study

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise;

    2015-01-01

    receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled......INTRODUCTION: Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1...... design. METHODS AND ANALYSIS: In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m(2)) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this...

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

    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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26431249

  2. Protamine-containing insulins are strong risk factors, and human insulin analogues are possible risk factors for insulin autoantibody: case-control study

    Hiroyuki Kinoshita

    2013-01-01

    Full Text Available Insulin autoantibody is known to cause fluctuation of blood glucose. We examined whether medications for diabetes are risk factors for insulin autoantibody. Especially, we examined the associations between types of insulin and insulin autoantibody. We performed a case-control study. From April 2005 to March 2010, insulin autoantibody was measured 273 times in 217 patients in our hospital. Insulin autoantibody was positive (greater than 10% 53 times in 19 patients (case, and was negative 220 times in 198 patients (control. Oral hypoglycemic agents were not risk factors for insulin autoantibody; the odds ratio was 0.0. In contrast, insulin use was a significant risk factor for insulin autoantibody; the odds ratio (95% confidence interval was 56.3 (7.3-432.5. As for the types of insulin and insulin autoantibody, human insulins without protamine were not risk factors; the odds ratio was 0.0. For protamine-containing insulins, the odds ratio and adjusted odds ratio (adjusted by age, gender, and disease: type 1 diabetes mellitus, type 2 diabetes mellitus, and no diabetes were 35.3 (9.6-129.5 and 29.6 (7.6- 115.4, respectively. For Aspart-containing insulins, they were 6.2 (2.2-17.9 and 3.8 (1.2- 12.0, respectively. For Glargine, they were 3.2 (0.6-16.7 and 1.3 (0.2-8.3, respectively. To decrease the problem of insulin antibody, avoiding the use of protamine-containing insulins and avoiding the use of human insulin analogues might be preferable for the patients with diabetes.

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

    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.

  4. Successful desensitization with human insulin in a patient with an insulin allergy and hypersensitivity to protamine: a case report

    Pföhler Claudia

    2008-08-01

    Full Text Available Abstract Introduction Insulin allergy may occur in patients treated with subcutaneous applications of insulin preparations. Besides additives in the insulin preparation such as protamine, cresol, and phenol, the insulin molecule itself may be the cause of the allergy. In the latter case, therapeutic options are rare. Case presentation A 68-year-old man with poorly controlled type 2 diabetes mellitus received different insulin preparations subcutaneously while on oral medication. Six to eight hours after each subcutaneous application, he developed pruritic plaques with a diameter of >15 cm at the injection sites that persisted for several days. Allergologic testing revealed positive reactions against every insulin preparation and against protamine. Investigation of serum samples demonstrated IgG antibodies against human and porcine insulin. We treated the patient with human insulin using an ultra-rush protocol beginning with 0.004 IU and a rapid augmentation in dose up to 5 IU. Therapy was accompanied by antihistamine therapy. Subsequent conversion to therapy with glargine insulin (6 IE twice daily was well-tolerated. Conclusion As reported in this case, desensitization with subcutaneously administered human insulin using an ultra-rush protocol in patients with an insulin allergy may present an easy form of therapy that is successful within a few days.

  5. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus.

    Oiknine, Ralph; Bernbaum, Marla; Mooradian, Arshag D

    2005-01-01

    Insulin is one of the oldest and best studied treatments for diabetes mellitus. Despite many improvements in the management of diabetes, the nonphysiological time-action profiles of conventional insulins remain a significant obstacle. However, the advent of recombinant DNA technology made it possible to overcome these limitations in the time-action profiles of conventional insulins. Used as prandial (e.g. insulin lispro or insulin aspart) and basal (e.g. insulin glargine) insulin, the analogues simulate physiological insulin profiles more closely than the older conventional insulins. If rapid-acting insulin analogues are used in the hospital, healthcare providers will need a new mind-set. Any error in coordination between timing of rapid-acting insulin administration and meal ingestion may result in hypoglycaemia. However, guidelines regarding in-hospital use of insulin analogues are few. The safety profile of insulin analogues is still not completely established in long-term clinical studies. Several studies have shown conflicting results with respect to the tumourigenic potential of this new class of agents. The clinical implications of these findings are not clear. Although novel insulin analogues are promising 'designer drugs' in our armamentarium to overcome some of the limitations of conventional insulin therapy, cost may be a limiting factor for some patients. PMID:15669878

  6. Review of insulin and its analogues in diabetes mellitus.

    Mane, Krishnappa; Chaluvaraju, Kc; Niranjan, Ms; Zaranappa, Tr; Manjuthej, Tr

    2012-03-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  7. IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy

    Freemantle, Nick; Mamdani, Muhammad; Vilsbøll, Tina; Kongsø, Jens Harald; Kvist, Kajsa; Bain, Stephen C

    2015-01-01

    = 225) [glucagon-like peptide-1 receptor agonist (GLP-1RA) add-on strategy]; basal-bolus (BB) insulin [insulin glargine (IGlar) + insulin aspart] (N = 56); or up-titration of IGlar (N = 329). A supplementary analysis was performed with the BB arm including patients who received IGlar or IDeg as basal......INTRODUCTION: IDegLira is a once-daily combination of insulin degludec (IDeg) and liraglutide. Trials directly comparing IDegLira with alternative strategies for intensifying basal insulin are ongoing. While awaiting results, this analysis compared indirectly how different strategies affected...... glycated hemoglobin (HbA1c) and other outcomes. METHODS: A pooled analysis of five completed Novo Nordisk randomized clinical trials in patients with type 2 diabetes inadequately controlled on basal insulin was used to compare indirectly IDegLira (N = 199) with: addition of liraglutide to basal insulin (N...

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

    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

  9. Insulin resistance and Alzheimer’s disease

    de la Monte, Suzanne M.

    2009-01-01

    Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer’s disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second maj...

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

    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...

  11. Insulin Secretagogues

    ... 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) ...

  12. Insulin allergy treated with human insulin (recombinant DNA).

    De Leeuw, I; Delvigne, C; Bekaert, J

    1982-01-01

    Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6-9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved. PMID:6765530

  13. Recombinant DNA technology in the treatment of diabetes: insulin analogs.

    Vajo, Z; Fawcett, J; Duckworth, W C

    2001-10-01

    After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed. PMID:11588149

  14. Influence of the dynamics of body weight on the risk factors of cardiovascular disease in patients with type 2 diabetes during the first year of insulin treatment

    T S Dzhavakhishvili

    2013-03-01

    Full Text Available The aim of the present study was to investigate whether insulin treatment-induced weight gain had an adverse impact on cardiovascular risk factors in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy when insulin analogues or human insulins are used. A total of 157 patients with newly insulinized type 2 diabetes were included in the study. The patients were divided in two groups. First group consisted of subjects (mean age 57 [45; 73], duration of diabetes of 10 years [4; 16] who had received long-acting basal (glargine, detemir, premixed (biphasic insulin aspart 30, Humalog Mix 25 or short-acting (aspart, lispro insulin analogues. Patients from second group (mean age 59 [46; 75], duration of diabetes of 10 years [5; 15] were treated with intermediate-acting basal (Protophane, Humulin NPH insulin, premixed (biphasic human insulin 30, Humulin M3 and regular (Actrapid, Humulin R human insulins. Our study has shown that insulin-induced weight gain may not adversely affect cardiovascular risk factors, particularly, lipid profile, in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy. Use of insulin analogues for treatment of type 2 diabetes patients results in better glycaemic control, significant declines in blood lipid concentrations, less increase in waist circumference compared with human insulins during the first year after initiating insulin therapy.

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

    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

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

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

    2016-01-01

    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. PMID:27600499

  17. Cost-effectiveness of intermediate or long-acting insulin versus Exenatide in type 2 diabetes mellitus patients not optimally controlled on dual oral diabetes medications

    Edwards KL

    2006-09-01

    Full Text Available Objective: To better understand exenatide’s role in the treatment of type 2 diabetes, this analysis assessed its cost-effectiveness in comparison to an intermediate (NPH and long-acting insulin (glargine. Exenatide is a recently approved medication for the treatment of type 2 diabetes for use in addition to frequently used oral diabetes medications. Methods: Two studies were identified by a Medline search (1996-Oct 2005 that were similar in study duration, baseline glycemic control, population size, and primary outcomes to appropriately assess the cost-effectiveness of either insulin in comparison to exenatide on both glycemic and weight control. Results: Both NPH and glargine appear to be more cost effective than exenatide with respect to glycemic control (incremental CE ratios -1,968 and -65,520 respectively. Exenatide appears to be more cost effective for reductions in body weight than either NPH (CE ratio 235 or glargine (CE ratio 128. Conclusions Compared to intermediate and long-acting insulin therapies, exenatide does not appear to be as cost effective for the treatment of type 2 diabetes.

  18. Insulin Test

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

  19. The role of insulin analogues in the current treatment of diabetes mellitus

    Mitrović Milena

    2006-01-01

    Full Text Available Introduction. Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion. Normal insulin secretion. In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis and stimulated (as a response to a meal. Conventional insulin preparations - human insulin, have time-action profiles that cannot fully imitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. Rapid-acting analogues. Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analouges, lispro and aspart are available. Basal insulin analogues. The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day, and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action. Mitogenic influence. The mitogenic influence of insulin is due to the affinity to bind to IGF-1 receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals. Conclusion. In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as

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

    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.

  1. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus

    Morello CM

    2011-12-01

    Full Text Available Candis M Morello1,21Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 2School of Pharmacy, University of California San Francisco, Veterans Affairs San Diego Healthcare System, San Diego, CA, USAIntroduction: The goal of insulin therapy in patients with either type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir and three rapid-acting insulins (aspart, lispro, and glulisine with improved pharmacokinetic/pharmacodynamic (PK/PD profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.Methods: This study reviews effects of the multiple demographic and clinical parameters in the insulin analogs glargine, detemir, lispro, aspart, and glulisine in patients with T2DM. A search was conducted on PubMed for each major topic considered (effects of injection site, age, race/ethnicity, obesity, renal or hepatic dysfunction, pregnancy, exercise, drug interactions using the topic words and name of each type of insulin analog. Information was also obtained from the prescribing information for each insulin analog.Results: The PK/PD profiles for insulin analogs may be influenced by many variables including age, weight, and hepatic and renal function. However, these variables do not have equivalent effects on all long-acting or rapid-acting insulin analogs.Conclusion: Rapid-acting and long-acting insulin analogs represent major advances in treatment for patients with T2DM who require insulin therapy. However, there are potentially important PK and PD differences between the two long-acting agents and among the three rapid-acting insulin analogs, which should be considered when designing treatment regimens for

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

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

    2008-01-01

    for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I m...... growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas...

  3. Effecttivity and safety of glargine treatment on perioperative patients with type 2 diabetes%甘精胰岛素用于2型糖尿病患者围手术期的疗效及安全性评价

    熊燕; 赖晓阳; 张美英

    2011-01-01

    Objective To observe the clinical effectivity and safety of Glargine treatment in perioperative patient with type 2 diabetes. Methods 60 T2DM patients scheduled for surgery were divided into glargine insulin group (Gla, n=30) and MDI group (Humulin N, n=30). The Dosage was adjusted according to a blood glucose fluctuations to compare the effect and safety between the two groups. Results The levels of blood glucose in the two groups were reduced after treatments (P<0. 01) and there is no significant difference in hypoglycemic effect between the two groups (P>0. 05). But the blood glucose fluctuation was smaller in Gla group than in MDI group and the glucose target arrival time was shorter in Gla group than in MDI group (P<0. 01). The insulin dosage, the incidences of hypoglycemia and wound infection and delayed healing rate were less in Gla group than in MDI group (P<0. 05). Conclusions Glargine treatment can effectively, rapidly and savely control the blood glucose and is especially suitable for the perioperative patient requiring a sufficient basal insulin.%目的 观察2型糖尿病(T2DM)患者围手术期甘精胰岛素治疗的临床疗效及安全性.方法 将60例拟行手术治疗的T2DM患者分为甘精胰岛素治疗组(Gla组,30例)及分次皮下注射胰岛素组(MDI组,30例),控制围手术期血糖.根据血糖监测结果调整药物剂量,比较2组患者降糖疗效及安全性.结果 两组均可有效降低血糖(P0.05).但Gla组血糖波动更小,达到良好血糖控制的所需时间明显缩短(P<0.01);Gla组胰岛素用量、低血糖发生率、切口感染或延迟愈合率均少于MDI组(P<0.05).结论 甘精胰岛素治疗能有效、安全、平稳、迅速地控制血糖,尤其适用于需要更有效补充基础胰岛素治疗阶段的糖尿病围手术期患者,值得临床推广运用.

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

    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

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

    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.

  6. [Insulin therapy for type 1 diabetes mellitus: past and present].

    Pires, Antonio Carlos; Chacra, Antonio Roberto

    2008-03-01

    The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells. PMID:18438537

  7. Insulin Injection

    ... placed in dosing pens. Be sure you know what type of container your insulin comes in and what other supplies, such as needles, syringes, or pens, ... name and letter on your insulin are exactly what your doctor prescribed.If ... a syringe marked for that type of insulin. Always use the same brand and ...

  8. Oral Insulin

    Kalra Sanjay; Kalra Bharti; Agrawal Navneet

    2010-01-01

    Abstract Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

  9. Biphasic Insulin Aspart 30/70: Pharmacokinetics and Pharmacodynamics Compared With Once-Daily Biphasic Human Insulin and Basal-Bolus Therapy

    Heise, Tim; Heinemann, Lutz; Hövelmann, Ulrike; Brauns, Bianca; Nosek, Leszek; Haahr, Hanne L.; Olsen, Klaus J.

    2009-01-01

    OBJECTIVE Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients. RESEARCH DESIGNS AND METHODS Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h. RESULTS Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg. CONCLUSIONS BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy. PMID:19487640

  10. Insulin resistance and hepatitis C

    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.

  11. Insulin detemir for the treatment of obese patients with type 2 diabetes

    Hollander PA

    2012-01-01

    Full Text Available Priscilla A Hollander1,21Baylor Endocrine Center, 2Baylor Medical Center, Dallas, Texas, USAAbstract: The risk for developing type 2 diabetes (T2DM is greater among obese individuals. Following onset of the disease, patients with T2DM become more likely to be afflicted with diabetic micro- and macrovascular complications. Decreasing body weight has been shown to lower glycosylated hemoglobin and improve other metabolic parameters in patients with T2DM. Medications used to lower blood glucose may increase body weight in patients with T2DM and this has been repeatedly shown to be the case for conventional, human insulin formulations. Insulin detemir is a neutral, soluble, long-acting insulin analog in which threonine-30 of the insulin B-chain is deleted, and the C-terminal lysine is acetylated with myristic acid, a C14 fatty acid chain. Insulin detemir binds to albumin, a property that enhances its pharmacokinetic/pharmacodynamic profile. Results from clinical trials have demonstrated that treatment with insulin detemir is associated with less weight gain than either insulin glargine or neutral protamine Hagedorn insulin. There are many potential reasons for the lower weight gain observed among patients treated with insulin detemir, including lower risk for hypoglycemia and therefore decreased defensive eating due to concern about this adverse event, along with other effects that may be related to the albumin binding of this insulin that may account for lower within-patient variability and consistent action. These might include faster transport across the blood–brain barrier, induction of satiety signaling in the brain, and preferential inhibition of hepatic glucose production versus peripheral glucose uptake. Experiments in diabetic rats have also indicated that insulin detemir increases adiponectin levels, which is associated with both weight loss and decreased eating.Keywords: basal insulin, body mass index, detemir, insulin analog, satiety

  12. Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study

    Ji L

    2016-08-01

    Full Text Available Linong Ji,1 Kyung Wan Min,2 Juliana Oliveira,3 Thomas Lew,4 Ran Duan3 1Department of Endocrinology, Peking University People's Hospital, Beijing, People's Republic of China; 2Department of Endocrinology, Eulji Hospital, Seoul, Republic of Korea; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Eli Lilly and Company, Taipei, Songshan District, Taiwan Objective: The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25] or insulin glargine plus insulin lispro (G+L in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups. Methods: Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130, Asian Indian (n=106, and East Asian (n=89. Results: All subgroups recorded glycated hemoglobin (HbA1c reductions: non-Asian (LM25, -2.07%; G+L, -2.05%, Asian Indian (LM25, -1.75%; G+L, -1.60%, and East Asian (LM25, -2.03%; G+L, -1.76%; end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2% and East Asians (LM25, 37.5%; G+L, 36.1% reached HbA1c ,7% versus non-Asians (LM25, 51.7%; G+L, 48.1%; differences were not significant (P=0.12 and P=0.06, respectively. The mean total daily insulin dose (U/kg for non-Asians was 0.67 (LM25 and 0.61 (G+L, for Asian Indians was 0.91 (LM25 and 0.90 (G+L, and for East Asians was 0.53 (LM25 and 0.59 (G+L. The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19±0.23, for Asian Indians was 0.33±0.25, and for East Asians was 0.34±0.27. Overall incidence (% of hypoglycemia in non-Asians was 94.1 (LM25 and 91.8 (G+L, in Asian Indians was 90.4 (LM25 and 88.5 (G+L, and in East Asians was 69.8 (LM25 and 77.3 (G+L. Conclusion: Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the

  13. Human insulin does not increase bladder cancer risk.

    Chin-Hsiao Tseng

    Full Text Available BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose were calculated and the hazard ratios were estimated by Cox regression. RESULTS: There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52% and 3,330 (0.48%, and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122-1.366], but not in the model adjusted for all covariates [1.063 (0.951-1.187]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. CONCLUSIONS: This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.

  14. Human Insulin Does Not Increase Bladder Cancer Risk

    Tseng, Chin-Hsiao

    2014-01-01

    Background Whether human insulin can induce bladder cancer is rarely studied. Methods The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression. Results There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. Conclusions This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication. PMID:24466131

  15. Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study

    Ji, Linong; Min, Kyung Wan; Oliveira, Juliana; Lew, Thomas; Duan, Ran

    2016-01-01

    Objective The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups. Methods Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89). Results All subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, −2.07%; G+L, −2.05%), Asian Indian (LM25, −1.75%; G+L, −1.60%), and East Asian (LM25, −2.03%; G+L, −1.76%); end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%) reached HbA1c <7% versus non-Asians (LM25, 51.7%; G+L, 48.1%); differences were not significant (P=0.12 and P=0.06, respectively). The mean total daily insulin dose (U/kg) for non-Asians was 0.67 (LM25) and 0.61 (G+L), for Asian Indians was 0.91 (LM25) and 0.90 (G+L), and for East Asians was 0.53 (LM25) and 0.59 (G+L). The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19±0.23, for Asian Indians was 0.33±0.25, and for East Asians was 0.34±0.27. Overall incidence (%) of hypoglycemia in non-Asians was 94.1 (LM25) and 91.8 (G+L), in Asian Indians was 90.4 (LM25) and 88.5 (G+L), and in East Asians was 69.8 (LM25) and 77.3 (G+L). Conclusion Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the LM25 arm with a lower rate of hypoglycemia. Asians required more mealtime insulin coverage than non-Asians. This study added important insight into the effect of ethnicity on insulin treatment outcomes in patients with type 2 diabetes.

  16. Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes

    Antonietta Colatrella; Natalia Visalli; Santina Abbruzzese; Sergio Leotta; Marzia Bongiovanni; Angela Napoli

    2013-01-01

    Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fastin...

  17. Newer insulin analogues and inhaled insulin

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  18. Insulin Injection

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Some ... or itching over the whole body shortness of breath wheezing dizziness blurred vision fast heartbeat sweating difficulty ...

  19. Hairy AdS Solitons

    Anabalon, Andres; Choque, David

    2016-01-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We discuss the role of these solutions for the existence of first order phase transitions for planar hairy black holes within these theories.

  20. Studies on insulin receptor, 2

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

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

    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

  2. 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

    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.

  3. 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.

    Rojas, Joselyn; Villalobos, Marjorie; Martínez, María Sofía; Chávez-Castillo, Mervin; Torres, Wheeler; Mejías, José Carlos; Miquilena, Edgar; Bermúdez, Valmore

    2014-01-01

    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. PMID:25548690

  4. Insulin dysfunction and Tau pathology

    Emmanuel Planel

    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.

  5. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    Pfohl, Martin

    2015-01-01

    Martin Pfohl,1 Thorsten Siegmund,2 Stefan Pscherer,3 Katrin Pegelow,4 Jochen Seufert5 1Medizinische Klinik I, Evangelisches Bethesda-Klinikum GmbH, Duisburg, Germany; 2Städtisches Klinikum München GmbH, Klinikum Bogenhausen, III. Medizinische Abteilung, München, Germany; 3Klinisches Diabeteszentrum Südostbayern, Innere Medizin – Diabetologie, Traunstein, Germany; 4Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 5Medizinische Universität...

  6. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    Pfohl M; Siegmund T; Pscherer S; Pegelow K; Seufert J

    2015-01-01

    Martin Pfohl,1 Thorsten Siegmund,2 Stefan Pscherer,3 Katrin Pegelow,4 Jochen Seufert5 1Medizinische Klinik I, Evangelisches Bethesda-Klinikum GmbH, Duisburg, Germany; 2Städtisches Klinikum München GmbH, Klinikum Bogenhausen, III. Medizinische Abteilung, München, Germany; 3Klinisches Diabeteszentrum Südostbayern, Innere Medizin – Diabetologie, Traunstein, Germany; 4Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 5Medizinische Universitätsklinik, Klinik für...

  7. Added Sugars

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... Learn more about reading food labels . Limit your consumption of foods with high amounts of added sugars, ...

  8. Wormholes in AdS

    Maldacena, Juan; Maoz, Liat

    2004-01-01

    We construct a few Euclidean supergravity solutions with multiple boundaries. We consider examples where the corresponding boundary field theory is well defined on each boundary. We point out that these configurations are puzzling from the AdS/CFT point of view. A proper understanding of the AdS/CFT dictionary for these cases might yield some information about the physics of closed universes.

  9. Adding Ajax

    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

  10. Alteration in insulin action

    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...

  11. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

  12. Newer insulin analogues and inhaled insulin

    Girish C

    2006-03-01

    Full Text Available Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera is recently approved by FDA and appears promising.

  13. Insulin Resistance and Prediabetes

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  14. Insulin Human Inhalation

    ... is a short-acting, man-made version of human insulin. Insulin inhalation works by replacing the insulin ... and selegiline (Eldepryl, Emsam, Zelapar); niacin; oral contraceptives (birth control pills); oral medications for diabetes such as pioglitazone ( ...

  15. Increased skeletal muscle capillarization enhances insulin sensitivity.

    Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

    2014-12-15

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we 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), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

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

    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.

  17. Relationships between cell surface insulin binding and endocytosis in adipocytes

    Chymotrypsin substrate analogues, such as N-acetyl-Tyr ethyl ester, have recently been demonstrated to inhibit the endocytic uptake of insulin in isolated rat adipocytes. In this study, the effect of N-acetyl-Tyr ethyl ester on cell surface insulin binding and dissociation were examined. Surface-bound 125I-insulin was distinguished from intracellular 125I-insulin by the sensitivity of the former to rapid dissociation with an acidic buffer. Plateau levels of surface-bound insulin at 37 degree C were increased 70% by inhibiting the internalization pathway. This increase was temperature and insulin concentration dependent. Thus differences in surface binding were small at 12 degree C and also at high insulin concentrations. Inhibition of internalization with N-acetyl-Tyr ethyl ester markedly slowed the loss of surface-bound insulin observed during dissociation the loss of surface-bound insulin observed during dissociation studies. After 20-30 min of dissociation, the remaining levels of surface-bound insulin were three- to fourfold higher in treated adipocytes compared with control adipocytes. Added unlabeled insulin retained its ability to accelerate the dissociation of insulin in N-acetyl-Tyr ethyl ester-treated cells. These observations indicate that the internalization pathway is a quantitatively important factor in determining levels of surface binding at 37 degree C and in determining the rat of deactivation of insulin binding

  18. Bone defect regeneration and cortical bone parameters of type 2 diabetic rats are improved by insulin therapy.

    Picke, A-K; Gordaliza Alaguero, I; Campbell, G M; Glüer, C-C; Salbach-Hirsch, J; Rauner, M; Hofbauer, L C; Hofbauer, C

    2016-01-01

    Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and display several features of human diabetic bone disease, including impaired osteoblast function, decreased bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treatment prevents skeletal complications associated with diabetes. Subcritical femur defects were created in diabetic (fa/fa) and non-diabetic (+/+) ZDF rats. Diabetic rats were treated once daily with long-lasting insulin glargin for 12weeks for glycemic control. Insulin treatment successfully maintained serum levels of glycated hemoglobin, while untreated diabetic rats showed a 2-fold increase. Trabecular and cortical bone mass measured by μCT were decreased in diabetic rats. Insulin treatment increased bone mass of the cortical, but not of the trabecular bone compartment. Dynamic histomorphometry revealed a lower bone formation rate at the trabecular and periosteal cortical bone in diabetic animals and decreased serum procollagen type 1 N-terminal propeptide (P1NP, -49%) levels. Insulin treatment partially improved these parameters. In T2DM, serum levels of tartrate-resistant acid phosphatase (TRAP, +32%) and C-terminal telopeptide (CTX, +49%) were increased. Insulin treatment further elevated TRAP levels, but did not affect CTX levels. While diabetes impaired bone defect healing, glycemic control with insulin fully reversed these negative effects. In conclusion, insulin treatment reversed the adverse effects of T2DM on bone defect regeneration in rats mainly by improving osteoblast function and bone formation. This article is part of a Special Issue entitled Bone and diabetes. PMID:26055107

  19. Determination of human insulin and its analogues in human blood using liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS).

    Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    The qualitative and quantitative determination of insulin from human blood samples is an emerging topic in doping controls as well as in other related disciplines (e.g. forensics). Beside the therapeutic use, insulin represents a prohibited, performance enhancing substance in sports drug testing. In both cases accurate, sensitive, specific, and unambiguous determination of the target peptide is of the utmost importance. The challenges concerning identifying insulins in blood by liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS) are detecting the basal concentrations of approximately 0.2 ng/mL and covering the hyperinsulinaemic clamps at > 3 ng/mL simultaneously using up to 200 μL of plasma or serum. This is achieved by immunoaffinity purification of the insulins with magnetic beads and subsequent separation by micro-scale liquid chromatography coupled to ion mobility / high resolution mass spectrometry. The method includes human insulin as well as the synthetic or animal analogues insulin aspart, glulisine, glargine, detemir, lispro, bovine, and porcine insulin. The method validation shows reliable results considering specificity, limit of detection (0.2 ng/mL except for detemir: 0.8 ng/mL), limit of quantification (0.5 ng/mL for human insulin), precision (CV  0.99), recovery, accuracy (>90%), robustness (plasma/serum), and ion suppression. For quantification of human insulin a labelled internal standard ([[(2) H10 ]-Leu(B6,B11,B15,B17) ] - human Insulin) is introduced. By means of the additional ion mobility separation of the different analogues, the chromatographic run time is shortened to 8 min without losing specificity. As proof-of-concept, the procedure was successfully applied to different blood specimens from diabetic patients receiving recombinant synthetic analogues. PMID:25219675

  20. Diabetes, insulin treatment, and cancer risk: what is the evidence?

    Azar, Madona; Lyons, Timothy J.

    2010-01-01

    Diabetes, in particular type 2, is associated with an increased incidence of cancer. Although the mortality attributable to cancer in type 2 diabetes is overshadowed by that due to cardiovascular disease, emerging data from epidemiologic studies suggest that insulin therapy may confer added risk for cancer, perhaps mediated by signaling through the IGF-1 (insulin-like growth factor-1) receptor. Co-administered metformin seems to mitigate the risk associated with insulin. A recent series of pu...

  1. NEWER STRATEGIES FOR INSULIN DELIVERY

    Singh Nisha; Lokwani Priyanka; Kaushik Avinash Yogendraji; Sharma Ritu

    2011-01-01

    Insulin is a proteinaceous hormone produced in the islets of Langerhans in the pancreas and used as a treatment in the diabetes mellitus. Successful oral insulin delivery involves overcoming the enzymatic and physical barriers and taking steps to conserve bioactivity during formulation processing. Newer strategies for insulin delivery include insulin pen injector, Refillable insulin injection pen, Insulin Syringe, Transfersome and Implantable insulin pumps.

  2. Insulin Resistance and Hyperinsulinemia

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  3. Autoantibodies against human insulin.

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

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

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

    2010-01-01

    Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and s...

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

    RobertRoot-Bernstein

    2014-01-01

    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 recepto...

  6. Insulin pumps.

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing to see more research on the psychosocial aspects of CSII during the year, both from the point of view of how psychological beliefs influence outcomes on CSII (is there a type of patient who does particularly well or poorly on CSII?) and how CSII affects psychological factors like mood, behaviour and quality of life. Quality of

  7. Intranasal insulin therapy

    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 was...

  8. Monoclonal antibodies to the insulin receptor mimic metabolic effects of insulin but do not stimulate receptor autophosphorylation in transfected NIH 3T3 fibroblasts

    The metabolic actions of insulin and anti-insulin receptor monoclonal antibodies were compared with their effects on insulin receptor phosphorylation in mouse NIH 3T3 fibroblasts transfected with human insulin receptor cDNA. In serum-starved NIH 3T3 HIR3.5 cells, uptake of 2-deoxy-[3H]glucose was stimulated up to 2-fold after 30 min with insulin, with a half-maximal effect at 0.1 nM insulin. Incorporation of [3H]thymidine was stimulated ∼ 12-fold after a 16-hr preincubation with insulin, with a half-maximal effect at 2 nM insulin. Phosphorylation of insulin receptor β-subunit in cells prelabeled with [32P]phosphate was increased 10- to 20-fold within 5 min of adding insulin. Monoclonal antibodies reacting with four different epitopes on the insulin receptor mimicked the effect of insulin on 2-deoxyglucose uptake. These antibodies also stimulated thymidine incorporation, although the maximum stimulation was only ∼ 30% that of insulin. It is concluded that the insulin-like metabolic effects of antibodies involve a mechanism of receptor activation that is independent of autophosphorylation and hence that receptor autophosphorylation is not an essential step in triggering at least some events in the insulin signaling pathway

  9. Generalised insulin oedema after intensification of treatment with insulin analogues

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  10. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli. PMID:12769691

  11. Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes.

    Han, Xiaojuan; Yang, Liling; Du, Heng; Sun, Qinjian; Wang, Xiang; Cong, Lin; Liu, Xiaohui; Yin, Ling; Li, Shan; Du, Yifeng

    2016-08-01

    The excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), mostly located on astrocytes, are the main mediators for glutamate clearance in humans. Malfunctions of these transporters may lead to excessive glutamate accumulation and subsequent excitotoxicity to neurons, which has been implicated in many kinds of neurodegenerative disorders including Alzheimer's disease (AD). Yet, the specific mechanism of the glutamate system dysregulation remains vague. To explore whether the insulin/protein kinase B (Akt)/EAAT signaling in human astrocytes could be disturbed by beta-amyloid protein (Aβ) and be protected by insulin, we incubated HA-1800 cells with varying concentrations of Aβ1-42 oligomers and insulin. Then the alterations of several key substrates in this signal transduction pathway were determined. Our results showed that expressions of insulin receptor, phospho-insulin receptor, phospho-protein kinase B, phospho-mammalian target of rapamycin, and EAAT1 and EAAT2 were decreased by the Aβ1-42 oligomers in a dose-dependent manner (p  0.05), and the mRNA levels of EAAT1 and EAAT2 were also unchanged (p > 0.05). Taken together, this study indicates that Aβ1-42 oligomers could cause disturbances in insulin/Akt/EAAT signaling in astrocytes, which might be responsible for AD onset and progression. Additionally, insulin can exert protective functions to the brain by modulating protein modifications or expressions. PMID:26358886

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

    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. PMID:25659889

  13. Giving an insulin injection

    ... medlineplus.gov/ency/patientinstructions/000660.htm Giving an insulin injection To use the sharing features on this ... and syringes. Filling the Syringe - One Type of Insulin Wash your hands with soap and water. Dry ...

  14. Insulin pump (image)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  15. Insulin Lispro Injection

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... sweating weakness muscle cramps abnormal heartbeat shortness of breath large weight gain in a short period of ...

  16. The Insulin Pump

    Toews, C. J.

    1985-01-01

    Subcutaneous continuous insulin infusion systems deliver insulin at a basal rate designed to keep blood glucose levels normal in the non-fed state. Additional insulin is delivered at meal time. Pumps can provide near optimal control of blood glucose concentrations in selected, highly motivated patients. The pump provides better diabetic control than once daily insulin injections, although several daily injections can provide comparable control. Optimal control with the pump causes some short-...

  17. Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes

    Antonietta Colatrella

    2013-01-01

    Full Text Available Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c, hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P<0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement.

  18. Insulin aspart pharmacokinetics

    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 and...

  19. Glycosphingolipids and insulin resistance

    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

  20. Intracellular pathways of insulin transport across vascular endothelial cells

    Processing and transport of hormones across vascular endothelial cells may modulate hormone action at subendothelial tissue sites. Insulin was transported across cultured rat capillary and bovine aortic endothelial cells, after a delay of 5-10 min, at a constant rate for 60 min at 37 degrees C. 125I-labeled insulin transport was inhibited by 88 +/- 11% (SE, n = 4) and 75 +/- 18% (SE, n = 4) in the presence of anti-insulin receptor antibody and unlabeled insulin (at 10(-7) M), respectively. Reverse phase high-performance liquid chromatography showed 88% of the 125I-insulin transported over 60 min was indistinguishable from the 125I-insulin added to the cells at 4 degrees C. In aortic endothelial cells preincubated with 2.3 x 10(-9) M of insulin for 24 h, insulin receptor binding was downregulated by 67%, and 125I-insulin transport was decreased by 52 +/- 11%. The proton ionophore monensin (0.05 mM) increased the internalized insulin in bovine aortic endothelial cells by 78%, with a corresponding decrease in 125I-insulin released by 76 +/- 2% (SE, n = 4). 125I-insulin transport across the aortic endothelial cell monolayer was similarly decreased (54 +/- 12%, SE, n = 4) by monensin. In contrast, the lysosomal protease inhibitor leupeptin had no effect. Degradation and transport were similarly dissociated by low temperature. At 15 degrees C, no significant insulin degradation was detected, whereas 125I-insulin release from the cells continued at 30 +/- 3% of the rate at 37 degrees C

  1. Online Ad Assignment with an Ad Exchange

    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...

  2. Insulin enhances glucose-stimulated insulin secretion in healthy humans

    Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Stefanovski, Darko; Bergman, Richard N.; Rogatsky, Eduard; Stein, Daniel T.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.

    2010-01-01

    Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) c...

  3. Metformin and insulin receptors

    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 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125I-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

  4. Two AdS2 branes in the euclidean AdS3

    We compute the density of open strings stretching between AdS2 branes in the euclidean AdS3. This is done by solving the factorization constraint of a degenerate boundary field, and the result is checked by a Cardy-type computation. We mention applications to branes in the minkowskian AdS3 and its cigar coset. (author)

  5. Two AdS2 branes in the Euclidean AdS3

    Ribault, S

    2003-01-01

    We compute the density of open strings stretching between AdS2 branes in the Euclidean AdS3. This is done by solving the factorization constraint of a degenerate boundary field, and the result is checked by a Cardy-type computation. We mention applications to branes in the Minkowskian AdS3 and its cigar coset.

  6. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu; Cao, Wenhong

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative s...

  7. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    RADERMECKER, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  8. Rat liver insulin receptor

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  9. Concentrated insulins: the new basal insulins

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    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 in...

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

    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.

  11. Classifying insulin regimens

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

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... 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...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the...

  12. Flexibility in insulin prescription

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage. PMID:27186563

  13. Flexibility in insulin prescription.

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage. PMID:27186563

  14. Flexibility in insulin prescription

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  15. Etiopathogenesis of insulin autoimmunity.

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  16. Insulin sensitivity and albuminuria

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

    2014-01-01

    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...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  17. AMPK and insulin action

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

    2013-01-01

    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...

  18. Human ultralente insulin.

    Holman, R R; Steemson, J; Darling, P; Reeves, W G; Turner, R.C.

    1984-01-01

    The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). Ther...

  19. Binding of insulin to rat pancreatic islets: comparison between pancreatic human insulin and biosynthetic human insulin

    Verspohl, E.J.; Ammon, H.P.

    Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.

  20. Anti-insulin antibody test

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  1. Alternative Devices for Taking Insulin

    ... KB). Alternate Language URL Alternative Devices for Taking Insulin Page Content On this page: What alternative devices ... the skin. [ Top ] What alternative devices for taking insulin are available? Insulin pens provide a convenient, easy- ...

  2. AdS solutions through transgression

    We present new classes of explicit supersymmetric AdS3 solutions of type IIB supergravity with non-vanishing five-form flux and AdS2 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 AdS3 solutions of type IIB supergravity and AdS2 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.)

  3. Polarised Black Holes in AdS

    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...

  4. Labile disulfide bonds in human placental insulin receptor.

    Finn, F. M.; Ridge, K D; HOFMANN, K

    1990-01-01

    The disulfide crosslinking pattern of human placental insulin receptor was investigated using selective reduction with tributylphosphine followed by alkylation with N-[3H]ethylmaleimide. Insulin receptor contains a single sulfhydryl group in each beta subunit whose alkylation with N-[3H]ethylmaleimide inhibits receptor autophosphorylation. Alkylation is partially inhibited by ATP or the nonhydrolyzable substrate analog adenosine 5'-[beta,gamma-imido]triphosphate when the nucleotides are added...

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

    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.

  6. Baby Skyrmions in AdS

    Elliot-Ripley, Matthew; Winyard, Thomas

    2015-01-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy...

  7. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  8. Insulin chewing gum: Need of the day for diabetic patients

    Mateti, Uday Venkat; Adla, Nagesh; Rajakannan, Thiyagu; Valakkathala, Rajesh

    2011-01-01

    Chewing gum is an excellent drug delivery system for self medication as it is convenient, can be administered discreetly without water and offers the removal of ‘needle fear’ for the patients. As it releases insulin orally, it helps in tackling of the deprivation of insulin by digestive enzyme without adding digestive enzyme inhibitor. This can be done by binding of vitamin B12 and insulin. The vitamin B12 is protected with haptocorrin which is a salivary protein. Another chemical pathway tak...

  9. Insulin Resistance of Puberty.

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID:27179965

  10. Diabetes, insulin and exercise

    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...... 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...... not be recommended as a means of improving metabolic control in insulin-dependent diabetes. However, our present knowledge and technology allows the well-informed and cooperative patient to exercise and even to reach the elite level. To achieve this, pre-exercise metabolic control should be optimal and knowledge...

  11. Insulin and the Lung

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

    2013-01-01

    , 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......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...... 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...

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

    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

  13. Is it dietary insulin?

    Vaarala, Outi

    2006-10-01

    In humans the primary trigger of insulin-specific immunity is a modified self-antigen, that is, dietary bovine insulin, which breaks neonatal tolerance to self-insulin. The immune response induced by bovine insulin spreads to react with human insulin. This primary immune response induced in the gut immune system is regulated by the mechanisms of oral tolerance. Genetic factors and environmental factors, such as the gut microflora, breast milk-derived factors, and enteral infections, control the development of oral tolerance. The age of host modifies the immune response to oral antigens because the permeability of the gut decreases with age and mucosal immune response, such as IgA response, develops with age. The factors that control the function of the gut immune system may either be protective from autoimmunity by supporting tolerance, or they may induce autoimmunity by abating tolerance to dietary insulin. There is accumulating evidence that the intestinal immune system is aberrant in children with type 1 diabetes (T1D). Intestinal immune activation and increased gut permeability are associated with T1D. These aberrancies may be responsible for the impaired control of tolerance to dietary insulin. Later in life, factors that activate insulin-specific immune cells derived from the gut may switch the response toward cytotoxic immunity. Viruses, which infect beta cells, may release autoantigens and potentiate their presentation by an infection-associated "danger signal." This kind of secondary immunization may cause functional changes in the dietary insulin primed immune cells, and lead to the infiltration of insulin-reactive T cells to the pancreatic islets. PMID:17130578

  14. Current status of AdS instability

    CERN. Geneva

    2016-01-01

    arXiv:1403.6471 and thoroughly developed in arXiv:1407.6273. On the other hand the negative cosmological constant allows for the existence of stable, time-periodic, asymptotically AdS solutions of Einstein equations [arXiv:1303.3186].

  15. Eternal Black Holes in AdS

    Maldacena, Juan M.

    2001-01-01

    We propose a dual non-perturbative description for maximally extended Schwarzschild Anti-de-Sitter spacetimes. The description involves two copies of the conformal field theory associated to the AdS spacetime and an initial entangled state. In this context we also discuss a version of the information loss paradox and its resolution.

  16. AdS braneworld with Backreaction

    Bilić Neven; Tupper Gary

    2013-01-01

    We review the tachyon model derived from the dynamics of a 3-brane moving in the AdS5 bulk. The bulk geometry is based on the Randall-Sundrum II model extended to include the radion. The effective tachyon Lagrangian is modified due to the back-reaction of the brane on the bulk geometry.

  17. AdS braneworld with Backreaction

    Bilic, Neven

    2014-01-01

    We review the tachyon model derived from the dynamics of a 3-brane moving in the AdS5 bulk. The bulk geometry is based on the Randall-Sundrum II model extended to include the radion. The effective tachyon Lagrangian is modified due to the back-reaction of the brane on the bulk geometry.

  18. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

    Ito H

    2014-04-01

    Full Text Available Hiroyuki Ito, Mariko Abe, Shinichi Antoku, Takashi Omoto, Masahiro Shinozaki, Shinya Nishio, Mizuo Mifune, Michiko ToganeDepartment of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, Tokyo, JapanBackground: The effects of switching from prandial premixed insulin therapy (PPT injected three times a day to basal plus two times bolus insulin therapy (B2B on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus.Methods: The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ was administered at the start and end of the study.Results: The glycated hemoglobin (HbA1c level (8.3%±1.8% to 8.2%±1.1% and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33% subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02. The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04.Conclusion: B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.Keywords: type 2 diabetes mellitus, insulin therapy, basal plus two times bolus insulin therapy, prandial premixed insulin therapy, Diabetes Treatment Satisfaction Questionnaire

  19. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with 125I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function

  20. Insulin Resistance and Hypertension

    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.

  1. Superradiant instability in AdS

    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.

  2. Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus

    Fournier, Marie

    2014-10-01

    Full Text Available [english] Objective: There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH-insulin in type 2 diabetes mellitus (T2DM patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs. Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT data with exenatide, insulin glargine and placebo as common references. Methods: A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA target and discontinuations due to adverse events (AEs were treated as binary variables, with risk ratios and odds ratios (ORs calculated. HbA and body weight were treated as continuous variables with difference in mean change from baseline (MD calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher’s method.Results: Seven RCTs (n=3,301 patients comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85] and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96] favouring lixisenatide over NPH-insulin and comparable changes in HbA from baseline (MD = 0.07%; 95% CI = [–0.26%, 0.41%]. In contrast to NPH-insulin

  3. A superactive insulin: [B10-aspartic acid]insulin(human).

    Schwartz, G P; Burke, G. T.; Katsoyannis, P G

    1987-01-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. We have synthesized a human insulin analogue, [AspB10]insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [AspB10]Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +/- 14...

  4. Insulin glulisine: insulin receptor signaling characteristics in vivo.

    Hennige, Anita M; Lehmann, Rainer; Weigert, Cora; Moeschel, Klaus; Schäuble, Myriam; Metzinger, Elisabeth; Lammers, Reiner; Häring, Hans-Ulrich

    2005-02-01

    In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (Lys(B3), Glu(B29)) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment. PMID:15677493

  5. Molecular mechanism of insulin resistance

    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.

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

    Conget, Ignacio; Battelino, Tadej; Giménez, Marga;

    2011-01-01

    injections. However, there is still a proportion of subjects using continuous subcutaneous insulin infusion in whom goals for metabolic control are far from achieved or benefits of this type of insulin therapy are transient. The SWITCH (Sensing With Insulin pump Therapy to Control HbA(1c) [hemoglobin A1c......]) 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....

  7. Insulin inhalation: NN 1998.

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  8. Instability corners in AdS space

    Dimitrakopoulos, Fotios V; Lippert, Matthew; Yang, I-Sheng

    2014-01-01

    We investigate whether arbitrarily small perturbations in global AdS space are generically unstable and collapse into black holes on the time scale set by gravitational interactions. We argue that current evidence, combined with our analysis, strongly suggests that a set of nonzero measure in the space of initial conditions does not collapse on this time scale. On the other hand, existing results do not provide an equally strong indication whether the unstable solutions also form a set of nonzero measure. We perform an analysis in position space to address this puzzle, and our formalism allows us to directly address the vanishing-amplitude limit. We show that gravitational self-interaction leads to tidal deformations which are equally likely to focus or defocus energy, and we sketch the phase diagram accordingly. We also clarify the connection between gravitational evolution in global AdS and holographic thermalization.

  9. Baby Skyrmions in AdS

    Elliot-Ripley, Matthew

    2015-01-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy models of holographic QCD) from an n layer to an n+1-layer configuration are observed at topological charges 9 and 27 and further popcorn transitions for higher charges are predicted. Finally, a point-particle approximation for the model is derived and used to successfully predict the ring structures and popcorn transitions for higher charge solitons.

  10. Boson Stars in AdS

    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 ...

  11. Conformal Mass in AdS gravity

    Jatkar, Dileep P; Miskovic, Olivera; Olea, Rodrigo

    2014-01-01

    We show that the Ashtekar-Magnon-Das (AMD) mass and other conserved quantities are equivalent to the Kounterterm charges in the asymptotically AdS spacetimes that satisfy the Einstein equations, if we assume the same asymptotic fall-off behavior of the Weyl tensor as considered by AMD. This therefore implies that, in all dimensions, the conformal mass can be directly derived from the bulk action and the boundary terms, which are written in terms of the extrinsic curvature.

  12. Insulin Resistance and Prediabetes

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  13. Insulin Resistance and Prediabetes

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  14. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  15. Etiopathogenesis of Insulin Autoimmunity

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  16. Conformational Dynamics of Insulin

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  17. Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

    Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

    2015-01-01

    Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, i...

  18. Refined holographic entanglement entropy for the AdS solitons and AdS black holes

    We consider the refinement of the holographic entanglement entropy for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss–Bonnet term. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy, the so-called renormalized entanglement entropy which is independent of the choices of UV cutoff. Our main results are: (i) the renormalized entanglement entropies of the AdSd+1 soliton for d=4,5 are neither monotonically decreasing along the RG flow nor positive-definite, especially around the deconfinement/confinement phase transition; (ii) there is no topological entanglement entropy for AdS5 soliton even with Gauss–Bonnet correction; (iii) for the AdS black holes, the renormalized entanglement entropy obeys an expected volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover even with Gauss–Bonnet correction; (iv) based on AdS/MERA conjecture, we postulate that the IR fixed-point state for the non-extremal AdS soliton is a trivial product state

  19. Predicting AD conversion

    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...

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

    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.

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

    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

  2. Winding Strings in AdS_3

    Minces, P; Minces, Pablo; Nunez, Carmen

    2006-01-01

    Correlation functions of one-unit spectral flowed states in string theory on AdS_3 are considered. We present a formalism which allows to explicitly find the modified Knizhnik-Zamolodchikov and null vector equations to be satisfied by amplitudes of states in w=1 sectors. We give a precise prescription to solve this system of linear differential equations in cases that are relevant to obtain three and four point functions involving spectral flowed string states. We specifically compute three point functions with two and three one-unit spectral flowed operators and also discuss four point functions.

  3. Insulin and Sex Interactions in Older Adults with Mild Cognitive Impairment

    Cholerton, Brenna; Baker, Laura D.; Trittschuh, Emily H.; Crane, Paul K.; Larson, Eric B.; Arbuckle, Matthew; Saucedo, Hector Hernandez; McCurry, Susan M.; Bowen, James D.; McCormick, Wayne C.; Craft, Suzanne

    2012-01-01

    Alzheimer’s disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. T...

  4. Molecular biocoding of insulin

    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

  5. Insulin receptor activation in the nucleus accumbens reflects nutritive value of a recently ingested meal.

    Woods, C A; Guttman, Z R; Huang, D; Kolaric, R A; Rabinowitsch, A I; Jones, K T; Cabeza de Vaca, S; Sclafani, A; Carr, K D

    2016-05-15

    With respect to feeding, insulin is typically thought of as a satiety hormone, acting in the hypothalamus to limit ingestive behavior. However, accumulating evidence suggests that insulin also has the ability to alter dopamine release in the striatum and influence food preferences. With increased access to high calorie foods, Western societies have a high prevalence of obesity, accompanied by insulin insensitivity. Little is known about how insulin is trafficked into the brain following food consumption and whether insulin insensitivity in the periphery is mirrored in the central nervous system. We investigated insulin receptor activation in the ventral striatum of rats receiving water or 16% glucose either orally or intragastrically. We also investigated whether glucose-induced insulin receptor activation was altered in food-restricted (FR) or diet-induced obesity (OB) rat models. Lastly, we examined whether insulin plays a significant role in flavor-nutrient preference learning. Glucose intake stimulated a rapid increase in insulin receptor activity in the ventral striatum of FR and ad libitum (AL) fed rats, but not OB rats. Similarly, both AL and FR, but not OB rats demonstrated significant flavor-nutrient preferences. However AL rats receiving brief inhibition of insulin activity during conditioning failed to acquire a significant flavor-nutrient preference. These findings suggest that impaired insulin receptor activation in the ventral striatum may result in inaccurate valuation of nutritive foods, which could lead to overconsumption of food or the selection of foods that don't accurately meet the body's current physiological needs. PMID:26988281

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

    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

  7. Probing crunching AdS cosmologies

    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.

  8. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin.

    Lopes, Marlene; Shrestha, Neha; Correia, Alexandra; Shahbazi, Mohammad-Ali; Sarmento, Bruno; Hirvonen, Jouni; Veiga, Francisco; Seiça, Raquel; Ribeiro, António; Santos, Hélder A

    2016-06-28

    The potential of nanoparticles (NPs) to overcome the barriers for oral delivery of protein drugs have led to the development of platforms capable of improving their bioavailability. However, despite the progresses in drug delivery technologies, the success of oral delivery of insulin remains elusive and the disclosure of insulin mechanisms of absorption remains to be clarified. To overcome multiple barriers faced by oral insulin and to enhance the insulin permeability across the intestinal epithelium, here insulin-loaded alginate/dextran sulfate (ADS)-NPs were formulated and dual-coated with chitosan (CS) and albumin (ALB). The nanosystem was characterized by its pH-sensitivity and mucoadhesivity, which enabled to prevent 70% of in vitro insulin release in simulated gastric conditions and allowed a sustained insulin release following the passage to simulated intestinal conditions. The pH and time-dependent morphology of the NPs was correlated to the release and permeation profile of insulin. Dual CS/ALB coating of the ADS-NPs demonstrated augmented intestinal interactions with the intestinal cells in comparison to the uncoated-NPs, resulting in a higher permeability of insulin across Caco-2/HT29-MTX/Raji B cell monolayers. The permeability of the insulin-loaded ALB-NPs was reduced after the temperature was decreased and after co-incubation with chlorpromazine, suggesting an active insulin transport by clathrin-mediated endocytosis. Moreover, the permeability inhibition with the pre-treatment with sodium chlorate suggested that the interaction between glycocalix and the NPs was critical for insulin permeation. Overall, the developed nanosystem has clinical potential for the oral delivery of insulin and therapy of type 1 diabetes mellitus. PMID:27074369

  9. Consumption of a High-Fat Diet Induces Central Insulin Resistance Independent of Adiposity

    Clegg, Deborah J.; Gotoh, Koro; Kemp, Christopher; Wortman, Matthew D.; Benoit, Stephen C.; Brown, Lynda M.; D’Alessio, David; Tso, Patrick; Seeley, Randy J.; Woods, Stephen C

    2011-01-01

    Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of...

  10. Diazoxide unmasks glucose inhibition of insulin release by counteracting entry of Ca2+

    The interaction of diazoxide with the effects of glucose on the insulin-releasing mechanism was analyzed in β-cell-rich pancreatic islets isolated from ob/ob mice. When added at a concentration of 400 μM to a medium containing 1.28 mM Ca2+, diazoxide converted glucose stimulation of insulin release into inhibition. Further addition of 2 mM theophylline restored the insulin secretory response to glucose. The paradoxical glucose inhibition of insulin release was accounted for by a diazoxide interaction with the entry of Ca2+, unmasking a capacity of the sugar to lower cytoplasmic Ca2+ below its resting concentration

  11. 3种新型长效胰岛素类似物%Three novel long acting human insulin analogs produced

    赵腾; 肖拥军; 曹春来; 彭韪

    2013-01-01

    The basal secretion of insulin is continuous low secretion. Regular human insulin secretion, the normal physiological insulin in diabetic patients can't rebuild a higher incidence of hypoglycemia, its clinical application. With the development of genetic engineering technology, the long-acting insulin analogues can simulate normal human insulin secretion after the injection for a small amount of release. Insulin glargine, detemir and degludec are all of human insulin analogs produced, although they are by changing the isoelectric point of insulin or increasing analogs molecular weight, to break down and absorption and extend the duration of action and simulate normal human insulin secretion, but having different molecular structure, long acting mechanisms, artworks and different clinical effects.%胰岛素的基础分泌是指其少量持续的分泌.常规人胰岛素由于不能很好地在糖尿病患者中重建正常生理性胰岛素分泌,低血糖发生率较高,影响了其临床应用.随着基因工程技术的发展,一批新出现的长效胰岛素类似物可以模拟正常人胰岛素的基础分泌,在注射后持续少量的释放.而目前3种新型的长效胰岛素类似物:甘精胰岛素、地特胰岛素和德谷胰岛素,虽然都通过改变胰岛素的等电点或增加类似物分子量的方法,使其分解、吸收及作用时间延长,更好地模拟正常人胰岛素的基础分泌,但其在分子结构、长效机制、生产工艺和临床使用上又有诸多不同.

  12. Adding Flavor to AdS4/CFT3

    Ammon, Martin; Meyer, Rene; O'Bannon, Andy; Wrase, Timm

    2009-01-01

    Aharony, Bergman, Jafferis, and Maldacena have proposed that the low-energy description of multiple M2-branes at a C4/Zk singularity is a (2+1)-dimensional N=6 supersymmetric U(Nc) x U(Nc) Chern-Simons matter theory, the ABJM theory. In the large-Nc limit, its holographic dual is supergravity in AdS4 x S7/Zk. We study various ways to add fields that transform in the fundamental representation of the gauge groups, i.e. flavor fields, to the ABJM theory. We work in a probe limit and perform analyses in both the supergravity and field theory descriptions. In the supergravity description we find a large class of supersymmetric embeddings of probe flavor branes. In the field theory description, we present a general method to determine the couplings of the flavor fields to the fields of the ABJM theory. We then study four examples in detail: codimension-zero N=3 supersymmetric flavor, described in supergravity by Kaluza-Klein monopoles or D6-branes; codimension-one N=(0,6) supersymmetric chiral flavor, described by...

  13. Ovarian tumors secreting insulin.

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  14. Insulin and carbohydrate dysregulation.

    Gelato, Marie C

    2003-04-01

    Patients with human immunodeficiency virus receiving highly active antiretroviral therapy (HAART) may experience abnormal body composition changes as well as metabolic abnormalities, including dyslipidemia, increases in triglycerides, low high-density lipoprotein cholesterol levels, and abnormal carbohydrate metabolism, ranging from insulin resistance with and without glucose intolerance to frank diabetes. Whether the body composition changes (i.e., increased visceral adiposity and fat wasting in the peripheral tissues) are linked to abnormalities in carbohydrate metabolism is unclear. The use of HAART with and without therapy with protease inhibitors (PIs) is related to carbohydrate abnormalities and changes in body composition. Regimens that include PIs appear to have a higher incidence of insulin resistance (up to 90%) and diabetes mellitus (up to 40%). The etiology of these abnormalities is not well understood; what is known about insulin and carbohydrate dysregulation with HAART is discussed. PMID:12652377

  15. Insulin C-peptide test

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

  16. Intranasal Insulin Prevents Anesthesia-Induced Spatial Learning and Memory Deficit in Mice

    Zhang, Yongli; Dai, Chun-ling; Chen, Yanxing; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2016-01-01

    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). At present, there is no treatment that can prevent anesthesia-induced postoperative cognitive dysfunction. Here, we treated mice with daily intranasal administration of insulin (1.75 U/day) for one week before anesthesia induced by intraperitoneal injection of propofol and maintained by inhalation of sevoflurane for 1 hr. We found that the insulin treatment prevented anesthesia-induced deficit in spatial learning and memory, as measured by Morris water maze task during 1–5 days after exposure to anesthesia. The insulin treatment also attenuated anesthesia-induced hyperphosphorylation of tau and promoted the expression of synaptic proteins and insulin signaling in the brain. These findings show a therapeutic potential of intranasal administration of insulin before surgery to reduce the risk of anesthesia-induced cognitive decline and AD. PMID:26879001

  17. Holography of AdS vacuum bubbles

    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.

  18. Twistor methods for AdS$_5$

    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.

  19. Probing crunching AdS cosmologies

    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...

  20. AdS3: the NHEK generation

    Bena, Iosif; Heurtier, Lucien; Puhm, Andrea

    2016-05-01

    It was argued in [1] 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× {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. Adipokines and Hepatic Insulin Resistance

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  2. Insulin-induced localized lipoatrophy:

    Breznik, Vesna; Kokol, Rok; Luzar, Boštjan; Miljković, Jovan

    2013-01-01

    Insulin lipoatrophy is a rare immunologic cutaneous complication in diabetes mellitus that presents with localized subcutaneous fat atrophy at the insulin injection site. We report the case of a 62-year-old woman with type 2 diabetes mellitus that developed localized lipoatrophy on the abdomen after 6 years of therapy with the insulin analogues detemir and aspart.

  3. Cinnamon, glucose and insulin sensitivity

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  4. Generation-dependent effect of PAMAM dendrimers on human insulin fibrillation and thermal stability.

    Nowacka, Olga; Milowska, Katarzyna; Belica-Pacha, Sylwia; Palecz, Bartlomiej; Šipošová, Katarina; Gazova, Zuzana; Bryszewska, Maria

    2016-01-01

    We have studied the effect of polyamidoamine (PAMAM) dendrimers of various generations on the thermal stability and fibrillation of human insulin. Thermostability of human insulin used differential scanning calorimetry (DSC), which showed two phase-transitions for insulin at 60 and 82°C. After adding dendrimers at 0.6 μmol/l, the first peaks disappeared and the second peaks were higher. We posited that, in the presence of dendrimers, the dimers in the solution were transformed into hexamers. The effect of dendrimers on insulin fibrillation was monitored by measuring ThT fluorescence, and visualization of insulin fibrils by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The effect of PAMAM dendrimers on insulin fibrillation was strongly dependent on the dendrimers generation and dendrimer:protein ratio. PMID:26598047

  5. Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease

    Osmanović Barilar, Jelena; Knezović, Ana; Grünblatt, Edna; Riederer, Peter; Šalković-Petrišić, Melita

    2015-01-01

    Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ≤3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ≤9 months...

  6. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  7. Insulin som trickster

    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...

  8. Polyethyleneglycol RIA (radioimmunoassay) insulin

    Insulin is a polypeptide hormone of M.W. 6,000 composed of two peptide chains, A and B, jointed by two cross-linked disulphide bonds and synthesized by the beta-cells of the islets of Langerhans of the pancreas. Insulin influences most of the metabolic functions of the body. Its best known action is to lower the blood glucose concentration by increasing the rate at which glucose is converted to glycogen in the liver and muscles and to fat in adipose tissue, by stimulating the rate of glucose metabolism and by depressing gluconeogenesis. Insulin stimulates the synthesis of proteins, DNA and RNA in cells generally, and promotes the uptake of aminoacids and their incorporation into muscle protein. It increases the uptake of glucose in adipose tissue and its conversion into fat and inhibits lipolysis. Insulin primary action is on the cell membrane, where it probably facilitates the transport of glucose and aminoacids into the cells. At the same time it may activate intracellular enzymes such as glycogen synthetase, concerned with glycogen synthesis. (Author)

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

    RobertRoot-Bernstein

    2014-07-01

    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.

  10. To observe and compare the effect of glycemic control in intensively treated adult subject with type 2 diabetes using insulin analogs and gene recombine human insulin%胰岛素类似物和重组人胰岛素强化治疗糖尿病观察

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

    2009-01-01

    Objective The study was designed to evaluate the clinical effectiveness and safety of glycose control using insulin analogs or gene recombine human insulin intensively treated adult subject with type 2 diabetes inadequately controlled with oral antidiabetes drugs. Methods This was 9 months open label randomized control trial involving 45 type 2 diabetes that needed using insulin assigned into two groups either using insulin analogs group or gene recombine human insulin group. Rapid-act insu-lin analogs lispro insulin or human regular insulin before each med plus long-act insulin analogs glargine or NPH insulin at bed-time was given subcutaneous injection quartic week respectively. Patients monitor blood glucose week by themselves, A1C was de-termine quarterly. Results Baseline A1C, diabetes duration and demography was similar in two groups. Mean A1C was significant-ly decreased insulin analogs group (-2.89±0.054)% ; recombine human insulin group (-2.32±0.052)% (P<0.05). Insulin analogs group showed superiority in A1C improvement (-0.57% ;P<0.01). A significantly higher number of subjects achieved Alc≤6.5% (52.17%vs 27.27%) and within target range was higher in the insulin analogs group(73.91% vs 45.45% ). Insulin does was similar, body weight was not significant differences between the two groups. Above target range glycemia were lower in the insulin analogs group. Nocturnal and severe hypoglycemia were lower in the insulin analogs group. Conclusion Our result shows that improved glycemic control can be gained and maintained over 9 months in patients with type 2 diabeties by using insulin analogs with no differece in dose and weight gain.%目的 比较胰岛素类似物和重组人胰岛素治疗成人2型糖尿病的疗效和安全性.方法 45例T2DM患者,分别给予超短效胰岛素类似物加长效胰岛素类似物或基因重组正规人胰岛素加精蛋白锌胰岛素强化治疗9个月,比较A1C、平均PG的达标率、低血糖和严重低血糖

  11. Insulin gene mutations and diabetes

    Nishi, Masahiro; Nanjo, Kishio

    2011-01-01

    Abstract Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four t...

  12. Insulin Modifies Honeybee Worker Behavior

    Christine M. Mott

    2012-10-01

    Full Text Available The insulin signaling pathway has been hypothesized to play a key role in regulation of worker social insect behavior. We tested whether insulin treatment has direct effects on worker honeybee behavior in two contexts, sucrose response thresholds in winter bees and the progression to foraging by summer nurse bees. Treatment of winter worker bees with bovine insulin, used as a proxy for honeybee insulin, increased the bees’ sucrose response threshold. Treatment of summer nurse bees with bovine insulin significantly decreased the age at which foraging was initiated. This work provides further insight into the role of endocrine controls in behavior of in honeybees and insects in general.

  13. ADS National Programmes: India

    Initial preliminary studies in India on ADS concepts were aimed toward applications such as, one way coupled booster reactor concept, thorium burner concept, enhancement of breeding rate of thorium– fueled fast reactors, and to incinerate Pu and minor actinides discharged from heavy water and fast reactors. These studies led to a roadmap on development of ADS subsystems in India, which was chalked out initially in June 2001. It was realized in these studies that the most challenging subsystem in terms of technology development and capital investment for ADS in India would be the high intensity proton accelerator, and that it must be accomplished in phased manner. Of the two alternative accelerator types, viz. the cyclotron and linear accelerator (linac), it is concluded that only linac would provide the necessary intense beam current for ADS applications. The energy amplifier (EA) scheme, with lead (45.5%) bismuth (55.5%) eutectic (LBE) as target & coolant, which was proposed in the early nineties would be one of the desired configurations of ADS for Indian applications. Additionally, subcritical reactor core of Indian Advanced Heavy Water Reactor (AHWR), with advantages of its low fission power density, and neutron economy is also a candidate among various ADS reactor configurations. These options of ADS configurations for thorium utilization are based on the neutronic properties of 233U isotope as fissile fuel, which are more or less similar in thermal and in moderately fast neutron spectra

  14. Adipocyte lipolysis and insulin resistance.

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. PMID:26542285

  15. Effect of Insulin Infusion on insulin-like growth factor I (IGF-I) during Hemodialysis

    Reinhard, Mark; Frystyk, Jan; Bjerre, Mette;

    2012-01-01

    Background: Hemodialysis (HD) is a catabolic procedure probably contributing to the high frequency of protein-energy wasting among patients on maintenance HD. The aim was to investigate the effect of insulin infusion on insulin-like growth factor I (IGF-I) during HD compared with a meal alone....... Methods: In a randomized cross-over study 11 non-diabetic HD patients (M/F:8/3, median age 57 years, range 33-79) received either 1) no treatment (NT), 2) glucose infusion (G) (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (GI) (10% glucose added 30 units of NovoRapid® per liter, 2.5 m......L/kg/h) during a standardized 4 h HD. During infusion, blood glucose levels were maintained at 8.0-10.0 mmol/L by additional glucose infusion. Glucose and glucose-insulin infusions were commenced 2 h prior to HD and continued throughout the HD session. Fasting blood samples were collected at baseline before...

  16. Managing diabetes with inhaled insulin

    Lucy D Mastrandrea

    2012-01-01

    Full Text Available The incidence of diabetes is increasing world-wide. Many individuals with diabetes require insulin to control their blood sugar and prevent both microvascular and macrovascular complications associated with this chronic disease. Current regimens involve delivery of subcutaneous insulin by injection or continuous insulin infusion. One area of research to advance diabetes care is aimed at developing alternate routes of insulin administration that will make daily management less invasive for patients. This review will focus on inhaled insulin, a novel formulation which takes advantage of drug delivery through the pulmonary system. The pharmacology, efficacy, and safety of inhaled insulin will be discussed. In addition, the status of inhaled insulin as a potential therapy for individuals with diabetes will be reviewed.

  17. Insulin degludec for diabetes mellitus.

    2013-07-01

    Over the last few years there has been a steady increase in the number of prescriptions dispensed in primary care for intermediate and long-acting insulin analogues and a reduction in prescriptions for biphasic isophane insulin. For example, in England, the volume of intermediate and long-acting insulin analogues in general practice has risen from approximately 650,000 prescriptions per quarter in 2007 to over 850,000 per quarter in 2012.(1) ▾Insulin degludec (Tresiba, Novo Nordisk) is a new long acting basal insulin analogue for the management of diabetes mellitus in adults.(2) Two strengths of insulin degludec (100 units/mL and 200 units/mL) were launched in the UK in February 2013. Here we discuss evidence for the effectiveness and safety of insulin degludec. PMID:23842634

  18. Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.

    Matthew D Campbell

    Full Text Available To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients.This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1 treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∼08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380±10 kcal and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, β-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal.All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05 resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≥8.0 mmol.l-1; 50% n = 6, Full n = 3. β-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = -0.484, p = 0.017.Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive

  19. Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

    Hallschmid, Manfred; Jauch-Chara, Kamila; Korn, Oliver; Mölle, Matthias; Rasch, Björn; Born, Jan; Schultes, Bernd; Kern, Werner

    2010-01-01

    OBJECTIVE In the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake. RESEARCH DESIGN AND METHODS Frontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU · kg−1 · min−1). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet. RESULTS Mean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging −372.2 μV from 21 to 90 min that was not observed during human insulin infusion (146.5 μV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04). CONCLUSIONS While inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake. PMID:20068139

  20. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively

  1. Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat

    Trinovita Andraini; Sophie Yolanda

    2015-01-01

    Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were ad...

  2. Superactive insulin: [B10-aspartic acid]insulin(human)

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, [Asp/sup B10/] insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [Asp/sup B10/] Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone

  3. Superactive insulin: (B10-aspartic acid)insulin(human)

    Schwartz, G.P.; Burke, G.T.; Katsoyannis, P.G.

    1987-09-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.

  4. Antiproton-Decelerator (AD)

    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.

  5. Value Adding Management

    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...

  6. Coopetitive Ad Auctions

    Hoy, Darrell; Jain, Kamal; Wilkens, Christopher A.

    2012-01-01

    A single advertisement often benefits many parties, for example, an ad for a Samsung laptop benefits Microsoft. We study this phenomenon in search advertising auctions and show that standard solutions, including the status quo ignorance of mutual benefit and a benefit-aware Vickrey-Clarke-Groves mechanism, perform poorly. In contrast, we show that an appropriate first-price auction has nice equilibria in a single-slot ad auction --- all equilibria that satisfy a natural cooperative envy-freen...

  7. AdS_3: the NHEK generation

    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.

  8. Hadronization at the AdS wall

    We describe hadronization events, using the AdS/CFT Correspondence, which display many of the qualitative features expected in QCD. In particular we study the motion of strings with separating end points in a back-reacted hard wall geometry. The solutions show the development of a linear QCD-like string. The end points oscillate in the absence of string breaking. We introduce string breaking by hand and evolve the new state forward in time to observe the separation of two string segments. A kink associated with this breaking evolves to the end points of the string inducing rho meson production. We explicitly compute the rho meson production at the end point.

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

    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

  10. Insulin receptor in Drosophila melanogaster

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-05-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound /sup 125/I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to /sup 125/I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to /sup 125/I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development.

  11. Insulin receptor in Drosophila melanogaster

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

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

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

    2015-01-01

    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

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

    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.

  14. AdS backgrounds from black hole horizons

    We utilize the classification of IIB horizons with 5-form flux to present a unified description for the geometry of AdSn, n = 3, 5, 7 solutions. In particular, we show that all such backgrounds can be constructed from eight-dimensional 2-strong Calabi–Yau geometries with torsion which admit some additional isometries. We explore the geometry of AdS3 and AdS5 solutions but we do not find AdS7 solutions. (paper)

  15. Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

    Jahangir, Zainab; Ahmad, Waqar; Shabbiri, Khadija

    2014-01-01

    Impaired insulin signaling has been thought of as important step in both Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Posttranslational modifications (PTMs) regulate functions and interaction of insulin with insulin receptors substrates (IRSs) and activate insulin signaling downstream pathways via autophosphorylation on several tyrosine (TYR) residues on IRSs. Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser) and threonine (Thr) residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation modification is important PTM and inhibits phosphorylation on same or neighboring Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been shown to be O-glycosylated; however exact sites are not determined yet. In this study, by using neuronal network based prediction methods, we found more than 50 Ser/Thr residues that have potential to be O-glycosylated and may act as possible sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1 Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize the risk of AD and T2DM. PMID:25580119

  16. Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

    Zainab Jahangir

    2014-01-01

    Full Text Available Impaired insulin signaling has been thought of as important step in both Alzheimer’s disease (AD and type 2 diabetes mellitus (T2DM. Posttranslational modifications (PTMs regulate functions and interaction of insulin with insulin receptors substrates (IRSs and activate insulin signaling downstream pathways via autophosphorylation on several tyrosine (TYR residues on IRSs. Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser and threonine (Thr residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation modification is important PTM and inhibits phosphorylation on same or neighboring Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been shown to be O-glycosylated; however exact sites are not determined yet. In this study, by using neuronal network based prediction methods, we found more than 50 Ser/Thr residues that have potential to be O-glycosylated and may act as possible sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1 Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize the risk of AD and T2DM.

  17. Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2

    ZHANG Yi; Zhou, Ben; Deng, Bo; Zhang, Fang; Wu, Jingxia; Wang, Yuangao; Le, Yingying; Zhai, Qiwei

    2013-01-01

    Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin to...

  18. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background. PMID:7968932

  19. ADS National Programmes: Italy

    Following a preliminary design developed in 1998, based on the Energy Amplifier concept proposed by CERN, a first configuration of a lead-bismuth Eutectic cooled Experimental ADS (LBE-XADS) was worked out in the period 1999–2001, under the aegis of MURST, by a group of Italian organizations led by Ansado Nucleare, with the aim of assessing the feasibility of a small sized (80 MWth) ADS. At the end of 1997 a joint effort of ENEA (National Agency for New Technology, Energy and the Environment) and INFN (National Institute for Nuclear Physics) led to the approval of a national programme by MURST (Minister for University and Scientific and Technological Research) named TRASCO (TRAsmutazione SCOrie) aiming at the study of physics and technologies needed to design an ADS for radioactive waste transmutation. The programme consisted of research subprogrammes on accelerator, neutronics, thermalhydraulics analysis, beam window technology, and material technology and compatibility with Pb and Pb-Bi. At now, most of the activities in support to the ADS development carried out at national level are part of EU-funded Projects. These activities are complemented by the programme agreement (AdP -Accordo di programma), signed between ENEA and the Ministry of Economic Development, which provides in general a range of activities aimed at the development of sustainable nuclear fission systems. Several universities and the national industry are involved, besides ENEA, in the activities

  20. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  1. Value Adding Management

    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...... impacts and strategic importance of FM for organisations and can be a practical tool for facilities managers in implementing value adding strategies and practices....... 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...

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

    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. PMID:20460925

  3. ADS National Programmes: China

    In China the conceptual study of an ADS concept which lasted for about five years ended in 1999. As one project of the National Basic Research Programme of China (973 Programme) in energy domain, which is sponsored by the China Ministry of Science and Technology (MOST), a five year programme of fundamental research of ADS physics and related technology was launched in 2000 and passed national review at the end of 2005. From 2007, another five year 973 Programme Key Technology Research of Accelerator Driven Subcritical System for Nuclear waste Transmutation started. The research activities were focused on HPPA physics and technology, reactor physics of external source driven subcritical assembly, nuclear data base and material study. For HPPA, a high current injector consisting of an ECR ion source, LEBT and an RFQ accelerating structure of 3.5 MeV has been built and were being improved. In reactor physics study, a series of neutron multiplication experimental study has been carrying out. The VENUS I facility has been constructed as the basic experimental platform for neutronics study in ADS blanket. VENUS I a zero power subcritical neutron multiplying assembly driven by external neutron produced by a pulsed neutron generator or 252Cf neutron source. The theoretical, experimental and simulation studies on nuclear data, material properties and nuclear fuel circulation related to ADS are carried out in order to provide the database for ADS system analysis. China Institute of Atomic Energy (CIAE), Institute of High Energy Physics (IHEP) and other Chinese institutes carried out the MOST project together. Besides CIAE, China Academy of Science (CAS) pays more and more attention to Advanced Nuclear Fuel Cycles (ANFC). A large programme of ANFC, including ADS and Th based nuclear fuel cycle, has been launched by CAS

  4. Gestational Diabetes Mellitus: Insulinic Management

    Magon, Navneet; Seshiah, Veerasamy

    2014-01-01

    Diabetic pregnancies have attendant risks. Adverse fetal, neonatal, and maternal outcomes in a diabetic pregnancy can be avoided by optimum glycemic control. Most pregnancies with GDM can be managed with non-insulinic management, which includes medical nutrition therapy. However, many necessitate concomitant insulinic management. The new insulin analogs present undoubted advantages in reducing the risk of hypoglycemia, mainly during the night, and in promoting a more physiologic glycemic prof...

  5. Protein Crystal Recombinant Human Insulin

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  6. Cell factories for insulin production

    Baeshen, Nabih A.; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Mohamed Morsi M. Ahmed; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M.

    2014-01-01

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host org...

  7. Nutritional Modulation of Insulin Resistance

    Weickert, Martin O.

    2012-01-01

    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 i...

  8. Dynamic ad hoc networks

    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

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

    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.

  10. ADS National Programmes: Belgium

    The Belgian activities in the field of Accelerator Driven Systems (ADS) are mainly related to the MYRRHA project development. MYRRHA is an accelerator driven, multi purpose fast neutron spectrum facility for R&D, cooled by a lead-bismuth eutectic. SCK•CEN has started the MYRRHA project as a national programme with several national & international bilateral collaboration agreements; the project has now evolved as an European integrated project in the frame of the IPEUROTRANS (European Commission, Sixth Framework Programme). The MYRRHA ‘Draft-2’ predesign file (completed in the early 2005) has been proposed to the partners as a basis for the XT-ADS machine. After a detailed investigation of potential alternatives, the MYRRHA concept (for the subcritical core, the primary coolant system, the accommodation of experimental rigs, the reactor vessel and the spallation target) has been kept with some modifications to achieve the XT-ADS objectives. The most recent version of the XT-ADS design was presented in the 2007 TWG meeting

  11. Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors.

    Keefer, L M; Piron, M A; DE MEYTS, P.

    1981-01-01

    Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, assoc...

  12. Specific uptake, dissociation, and degradation of 125I-labeled insulin in isolated turtle (Chrysemys dorbigni) thyroid glands

    Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with 125I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of bovine insulin that inhibited 50% of the 125I-insulin uptake was 2 micrograms/ml of incubation medium. Most of the radioactive material (71%) extracted from the gland, after 30 min incubation with 125I-insulin, eluted in the same position as labeled insulin on Sephadex G-50. Only 24% eluted in the salt position. After 240 min incubation, increased amount of radioactivity appeared in the Na125I position. When bovine insulin was added together with the labeled hormone, a substantial reduction of radioactivity was observed in the insulin and Na125I elution positions. Dissociation studies were performed at 6 degrees in glands preincubated with 125I-insulin either at 24 or 6 degrees. The percentage of trichloroacetic acid (TCA)-soluble radioactive material in the dissociation medium increased with incubation time at both temperatures. However, the degradation activity was lower at 6 than at 24 degrees. The addition of bovine insulin to the incubation buffer containing 125I-insulin reduced the radioactive degradation products in the dissociated medium. Chloroquine or bacitracin inhibited the degradation activity. Incubation of thyroid glands with 125I-hGH or 125I-BSA showed values of uptake, dissociation, and degradation similar to those experiments in which an excess of bovine insulin was added together with the labeled hormone. Thus, by multiple criteria, such as specific uptake, dissociation, and degradation, the presence of insulin-binding sites in the turtle thyroid gland may be suggested

  13. SIRT2 regulates insulin sensitivity in insulin resistant neuronal cells.

    Arora, Amita; Dey, Chinmoy Sankar

    2016-06-10

    Insulin resistance in brain is well-associated with pathophysiology of deficits in whole-body energy metabolism, neurodegenerative diseases etc. Among the seven sirtuins, SIRT2 is the major deacetylase expressed in brain. Inhibition of SIRT2 confers neuroprotection in case of Parkinson's disease (PD) and Huntington's disease (HD). However, the role of this sirtuin in neuronal insulin resistance is not known. In this study, we report the role of SIRT2 in regulating insulin-sensitivity in neuronal cells in vitro. Using approaches like pharmacological inhibition of SIRT2, siRNA mediated SIRT2 knockdown and over-expression of wild-type and catalytically-mutated SIRT2, we observed that downregulation of SIRT2 ameliorated the reduced activity of AKT and increased insulin-stimulated glucose uptake in insulin resistant neuro-2a cells. The data was supported by over expression of catalytically-inactive SIRT2 in insulin-resistant human SH-SY5Y neuronal cells. Data highlights a crucial role of SIRT2 in regulation of neuronal insulin sensitivity under insulin resistant condition. PMID:27163642

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

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part of the ...

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

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

    2015-01-01

    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 GLP-1 RA treatment on body weight, glycaemic control and total daily insulin dose in obese, insulin-using type 2 diabetes patients after 2 years follow-up in a real life setting and to explore a poss...

  16. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  17. Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity.

    Eckel, Robert H; Depner, Christopher M; Perreault, Leigh; Markwald, Rachel R; Smith, Mark R; McHill, Andrew W; Higgins, Janine; Melanson, Edward L; Wright, Kenneth P

    2015-11-16

    Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration. PMID:26549253

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

    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.

  19. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L.; Kanekiyo, Takahisa; Bu, Guojun

    2015-01-01

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes durin...

  20. Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.

    Gupta, Vivek; Hwang, Byeong-Hee; Doshi, Nishit; Banerjee, Amrita; Anselmo, Aaron C; Mitragotri, Samir

    2016-06-01

    A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence. PMID:26864536

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

    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. ADS National Programmes: Japan

    In Japan, the research and development (R&D) activities on partitioning and transmutation (P&T) technology had been promoted under the OMEGA programme since 1988. The main institutes involved in these activities were the Japan Atomic Energy Research Institute (JAERI), the Japan Nuclear Cycle Development Institute (JNC), and the Central Research Institute of Electric Power Industry (CRIEPI). Among these institutes, JAERI had mainly conducted the R&D on ADS. In 1999 and 2000, the Atomic Energy Commission (AEC) of Japan implemented the check and review (C&R) on the P&T technology, and the ADS was considered as one of candidates for transmutation systems together with fast reactors. In 2005, JAERI and JNC were merged and the Japan Atomic Energy Agency (JAEA) was established. In JAEA, the R&D activities on both ADS and fast reactors have been continued. In August, 2008, the AEC of Japan launched the Technical Subcommittee on P&T Technology under the Advisory Committee on R&D, and conducted the discussion about the current state of the art concerning P&T technology in Japan and the future R&D programme. The Subcommittee issued the final report in April, 2009. The final report covered the impact of the P&T technology, the state of the art of the technology, evaluation on the progress of the R&D, and the recommendations of the future R&D. As the basic policy on the P&T technology, the report stated that the R&D should not aim at only the improvement of the P&T performance, but at the achievement of the requirements for whole performance of nuclear power generation. This means that the performance of the Double strata fuel cycle concept should be evaluated from viewpoints of safety, economy, environmental friendliness, saving resource, and non-proliferation of the first stratum as well as those of the second stratum. The Double strata concept, therefore, should be studied as a part of the whole nuclear system both in the transient phase of LWR to FBR and the equilibrium

  3. Management job ads

    Holmgreen, Lise-Lotte

    2014-01-01

    jobs by discursively constructing job ads that appeal to both sexes. This argument is part of the broader field of corporate social responsibility, corporate citizenship, and stakeholder management, which involves discussions of the obligations of corporations to acknowledge and mitigate the......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...... increasingly widespread impact that their activities have on communities and social structures. The article emphasises the need for more active engagement on the part of corporations by analysing the discursive construction of preferred candidates in a small sample of Danish management job ads. By means of...

  4. Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle.

    Keogh, Kate; Kenny, David A; Kelly, Alan K; Waters, Sinéad M

    2015-08-01

    The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days (period 1) (RES, n = 15) followed by ad libitum feeding for 55 days (period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P alimentation (P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth. PMID:26015430

  5. Adding linear orders

    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.

  6. ADS National Programmes: France

    Studies related to nuclear reactors and radioactive waste started at the French National Centre for Scientific research, CNRS, as a result of the French law on radioactive waste that was published in 1991. They were initially organized around the programme PACE (Physique pour l’Aval du Cycle Electronucléaire = physics of the back end of the nuclear fuel cycle), which became PACEN (Physique pour l’Aval du Cycle et production d’Energie Nucléaire = Physics of the back end of the nuclear fuel cycle and production of nuclear energy) in 2006. Research on accelerator driven systems was from the beginning part of this programme. This research is mainly funded by the National Institute for Nuclear end Particle Physics (IN2P3) of CNRS and within the EURATOM European programmes (FP5, 6 and 7). The programme took place in several stages, and covered various scientific fields, benefitting from expertise of CNRS in the field. More specifically, it aimed and still aims to: – Test and verify the feasibility and design of the ADS concept, in terms of neutronics, physics of materials, design of the accelerator and tests of its prototypical components that have been built (or are at present under construction); – Measure and-or improve nuclear data related to radioactive waste transmutation. Today, most of the activities in support to ADS development carried out by CNRS focus on accelerator developments, GUINEVERE (Generator of Uninterrupted Intense NEutron at the lead VEnus REactor) experiment, ADS core studies, deployment scenarios and nuclear data measurements. The CEA R&D programmes on ADS are mainly focused on the European project EUROTRANS of the 6th Framework programme (2005–2010) and continued in the FREYA project of the 7th Framework Programme

  7. Additional disulfide bonds in insulin

    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...... higher yields 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...... predicts four additional four disulfide insulin analogues which could be expressed. Although the location of the additional disulfide bonds is only slightly shifted, this shift impacts both stability and activity of the resulting insulin analogues....

  8. AdS 3-manifolds and Higgs bundles

    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...

  9. When Intensive Insulin Therapy (MDI) Fails in Patients With Type 2 Diabetes: Switching to GLP-1 Receptor Agonist Versus Insulin Pump.

    Cohen, Ohad; Filetti, Sebastiano; Castañeda, Javier; Maranghi, Marianna; Glandt, Mariela

    2016-08-01

    Treatment with insulin, alone or with oral or injectable hypoglycemic agents, is becoming increasingly common in patients with type 2 diabetes. However, approximately 40% of patients fail to reach their glycemic targets with the initially prescribed regimen and require intensification of insulin therapy, which increases the risks of weight gain and hypoglycemia. Many of these patients eventually reach a state in which further increases in the insulin dosage fail to improve glycemic control while increasing the risks of weight gain and hypoglycemia. The recently completed OpT2mise clinical trial showed that continuous subcutaneous insulin infusion (CSII) is more effective in reducing glycated hemoglobin (HbA1c) than intensification of multiple daily injection (MDI) insulin therapy in patients with type 2 diabetes who do not respond to intensive insulin therapy. CSII therapy may also be useful in patients who do not reach glycemic targets despite multidrug therapy with basal-bolus insulin and other agents, including glucagon-like peptide (GLP)-1 receptor agonists; current guidelines offer no recommendations for the treatment of such patients. Importantly, insulin and GLP-1 receptor agonists have complementary effects on glycemia and, hence, can be used either sequentially or in combination in the initial management of diabetes. Patients who have not previously failed GLP-1 receptor agonist therapy may show reduction in weight and insulin dose, in addition to moderate improvement in HbA1c, when GLP-1 receptor agonist therapy is added to MDI regimens. In subjects with long-standing type 2 diabetes who do not respond to intensive insulin therapies, switching from MDI to CSII and/or the addition of GLP-1 receptor agonists to MDI have the potential to improve glycemic control without increasing the risk of adverse events. PMID:27440831

  10. Evaporation of large black holes in AdS

    The AdS/CFT correspondence offers a new perspective on the long-standing black hole information paradox. However, to be able to use the available gauge/gravity machinery one is forced to consider so-called 'large' black holes in AdS, and these objects are thermodynamically stable - they do not evaporate. We describe a simple toy model that allows large AdS black holes to decay, by coupling the emitted radiation to an external scalar field propagating in an auxiliary space. This effectively changes the properties of the boundary of AdS, making it partly absorbing. We demonstrate that the evaporation process never ceases by explicitly presenting (a) the transmission coefficient for a wave scattering from the bulk into auxiliary space and (b) the greybody factor for a black 3-brane in an AdS background. Therefore, the model provides an interesting framework to address the information paradox using AdS/CFT techniques.

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

    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.

  12. Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

    It was reported two decades ago that insulin was not detectable in the glucose-stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled park insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report the authors describe the purification and amino acid sequences of squirrel monkey insulin and glucagon. They demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in their immunoassay system is only a few percent of that of human insulin. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species

  13. Measurement of insulin in human sera using a new RIA kit. 1

    A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 ± 2.0% (n = 38) and 100.1 ± 1.9% (n = 42), respectively. In addition to human insulin, procine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40 % on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated. (author)

  14. Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

    Yu, Jinghua (Veterans Administration Medical Center, Bronx, NY (United States)); Eng, J.; Yalow, R.S. (Veterans Administration Medical Center, Bronx, NY (United States) City Univ. of New York, NY (United States))

    1990-12-01

    It was reported two decades ago that insulin was not detectable in the glucose-stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled park insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report the authors describe the purification and amino acid sequences of squirrel monkey insulin and glucagon. They demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in their immunoassay system is only a few percent of that of human insulin. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species.

  15. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Tina Sartorius

    Full Text Available OBJECTIVES: Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. METHODS: Cinnamon components (eugenol, cinnamaldehyde were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. RESULTS: Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. CONCLUSIONS: Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  16. The effect of Ad

    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.

  17. Eating ad Libitum

    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...... producing an eater who: ”shouldn't restrain herself”. Practices of food and eating in the test meal I suggest, will allow us to tackle reductionism by showing the complex cultural context shaping clinical intervention....

  18. Optimizing the insulin therapy in patients with T2DM: More safety and efficiency%优化胰岛素治疗让2型糖尿病患者更安全获益

    彭永德

    2012-01-01

    2009年美国糖尿病学会(ADA)和欧洲糖尿病研究学会(EASD)关于T2DM治疗的共识,及2007年中国糖尿病治疗指南均指出,生活方式干预和优化口服降糖药(OAD)控制血糖不佳时,应首选基础胰岛素治疗.但在临床实践中,预混胰岛素联合1~2种OADs治疗方案占目前胰岛素治疗的主导地位.研究显示,既往预混胰岛素控制不佳的患者转换成甘精胰岛素加OADs继续治疗时,血糖进一步改善.转换治疗后注射次数少,使用简便,同时体重无增加,因此患者满意度明显提高.%The consensus of 2009 ADA/EASD and 2007 Chinese Diabetes Society recommend that type 2 diabetes patients should initiate basal insulin therapy when life-style intervention and metformin combination therapy is failure. But in clinical practice, twice daily premix insulin combined with 1 ~ 2 OADs treatment is the leading regimen. Studies showed that type 2 diabetic patients previously uncontrolled by premix insulin, switching to glargine insulin plus OADs regimen can lead to further-controlled blood glucose, with less frequency of injection, being easier to use, less weight gain, and better treatment satisfaction of patients.

  19. 21 CFR 522.1160 - Insulin.

    2010-04-01

    ...) of insulin. (2) Each mL of protamine zinc recombinant human insulin suspension contains 40 IU of... control has been attained. (B) Protamine zinc recombinant human insulin. Administer an initial dose of 0.1... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and...

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

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

    1985-01-01

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

  1. Alternative routes of insulin delivery

    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.

  2. Dirac operator on fuzzy AdS2

    In this article we construct the chirality and Dirac operators on fuzzy AdS2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated to AdS2. It is shown that the degeneracy of the spectrum present in the commutative AdS2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space. (author)

  3. Dirac Operator on Noncommutative AdS_2

    Fakhri, H

    2003-01-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS_2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated with AdS_2. It is shown that the degeneracy of the spectrum present in the commutative AdS_2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  4. Dirac operator on fuzzy AdS2

    Fakhri, Hossein; Imaanpur, Ali

    2003-03-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated to AdS2. It is shown that the degeneracy of the spectrum present in the commutative AdS2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  5. Dirac Operator on Fuzzy AdS_2

    H. Fakhri; Imaanpur, A.

    2003-01-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS_2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated with AdS_2. It is shown that the degeneracy of the spectrum present in the commutative AdS_2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  6. Radius-dependent gauge unification in AdS5

    Choi, Kiwoon; Kim, Hyung Do; Kim, Ian-Woo

    2002-01-01

    We examine the relation of the 4-dimensional low energy coupling of bulk gauge boson in a slice of AdS5 to the 5-dimensional fundamental couplings as a function of the orbifold radius R. This allows us to address the gauge coupling unification in AdS5 by means of the radius running as well as the conventional momentum running. We then compute the radius dependence of 1-loop low energy couplings in generic AdS5 theory with 4-dimensional supersymmetry, and discuss the low energy predictions whe...

  7. Open Strings on AdS_2 Branes

    Lee, Peter; Ooguri, Hirosi; Park, Jongwon; Tannenhauser, Jonathan

    2001-01-01

    We study the spectrum of open strings on AdS_2 branes in AdS_3 in an NS-NS background, using the SL(2,R) WZW model. When the brane carries no fundamental string charge, the open string spectrum is the holomorphic square root of the spectrum of closed strings in AdS_3. It contains short and long strings, and is invariant under spectral flow. When the brane carries fundamental string charge, the open string spectrum again contains short and long strings in all winding sectors. However, branes w...

  8. Thermodynamics of Asymptotically Locally AdS Spacetimes

    Papadimitriou, I; Papadimitriou, Ioannis; Skenderis, Kostas

    2005-01-01

    We formulate the variational problem for AdS gravity with Dirichlet boundary conditions and demonstrate that the covariant counterterms are necessary to make the variational problem well-posed. The holographic charges associated with asymptotic symmetries are then rederived via Noether's theorem and `covariant phase space' techniques. This allows us to prove the first law of black hole mechanics for general asymptotically locally AdS black hole spacetimes. We illustrate our discussion by computing the conserved charges and verifying the first law for the four dimensional Kerr-Newman-AdS and the five dimensional Kerr-AdS black holes.

  9. Killing spinors and supersymmetry on AdS

    In this paper we construct several supersymmetric theories on AdS5 background. We discuss the proper definition of the Killing equation for the symplectic Majorana spinors required in AdS5 supersymmetric theories. We find that the symplectic Killing spinor equation involves a matrix M in the USp(2N) indices whose role was not recognized previously. Using the correct Killing spinors we explicitly confirm that the particle masses in the constructed theories agree with the predictions of the AdS/CFT correspondence. Finally, we establish correct O(d - 1,2) isometry transformations required to keep the Lagrangian invariant on AdSd

  10. Cutaneous allergy to human (recombinant DNA) insulin.

    Grammer, L C; Metzger, B E; Patterson, R

    1984-03-16

    p6 report two cases of cutaneous allergy to human (recombinant DNA) insulin. Each patient had a history of systemic allergic reactions to porcine insulin and was at least as reactive to human as to porcine insulin by end-point cutaneous titration. Both patients' insulin allergy was managed with animal insulins and both have done well. Our experience with these two patients indicates that human insulin (rDNA) should not be expected to be efficacious in all patients with systemic allergy to insulin. PMID:6366262

  11. New ways of insulin delivery.

    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

  12. Redox Regulation of Insulin Degradation by Insulin-Degrading Enzyme

    Cordes, Crystal M.; Bennett, Robert G.; Siford, Gerri L.; Hamel, Frederick G.

    2011-01-01

    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 ...

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

    Lucy D Mastrandrea

    2010-01-01

    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 contro...

  14. Basal insulin regime change from Lantus to Toujeo resulted in fewer hypoglycaemic episodes in a 28-year-old man with diabetes mellitus.

    Shields, Alexandra; Sankaranarayanan, Sailesh

    2016-01-01

    An active 28-year-old man with type 1 diabetes mellitus reported a reduced number of hypoglycaemic episodes following change in basal regime insulin glargine from U100 Lantus to U300 Toujeo. Consequently, an improved quality of life was also reported. Flash-based glucose monitoring was utilised to record 24-hour continuous glucose levels throughout two comparable 60-day periods before and after the change in regimen. Low blood glucose was most likely between 03:00 and 08:00. Nocturnal hypoglycaemic episodes (≤3.9 mmol/L) reduced by an average of 2.5 episodes per week. Severe hypoglycaemic episodes (≤2.9 mmol/L) reduced to an average of 0.4 per week, down from 1.5 per week. Nocturnal hypoglycaemic episodes reduced in frequency and severity. Furthermore, nocturnal hypoglycaemia episodes occurred in a more predictable time window. This was especially important in the reported reduction of impact on the patient's quality of life, as the episodes tended to be associated with anxiety and low mood. Patient education needed to facilitate this change was minimal, and benefits to the patient were great, including decreased sleep disturbances and reduced risk of associated anxiety symptoms. PMID:27307429

  15. Conical singularities in AdS space time

    Full text: In recent years, the study of conformal gauge theories from 10-D has been motivated by the AdSd+1/CFTd correspondence, first conjectured by J. Maldacena. The aim of this work is to consider the d = 4 case by analysing the configuration of the N coincident D3 branes. In this context, the work shows that there is a duality between type IIB string theory in AdS5 x S5 and N = 4 SU(N) Super Yang-Mills Theory in the IR. The AdS5/CFT4 correspondence brought also new approaches to the strong coupling problem in QCD. Nowadays, there is a whole line of works that focus on the low dimensional correspondence AdS4/CFT3, like the application to graphene and topological insulators, and the AdS3/CFT2 correspondence, related with the entanglement entropy. In this work, we consider the vortex configuration solution to the AdS4 and AdS3 space-time. The most important motivation is to discuss the boundary theory resulting from these solutions. We have examined a straightforward approach to a holographic computation of the graphene and entanglement entropy in the presence of the conical singularity. After this analysis, we consider the scalar field in the bulk in the presence of this metrics and work out the compactification modes. Taking the holographic point of view, we study and discuss the resulting Green function. (author)

  16. Current european regulatory perspectives on insulin analogues

    Enzmann Harald G; Weise Martina

    2011-01-01

    Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing aut...

  17. Wireless Ad Hoc Networks

    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.

  18. Thermodynamics of large AdS black holes

    We consider leading order quantum corrections to the geometry of large AdS black holes in a spherical reduction of four-dimensional Einstein gravity with negative cosmological constant. The Hawking temperature grows without bound with increasing black hole mass, yet the semiclassical back-reaction on the geometry is relatively mild, indicating that observers in free fall outside a large AdS black hole never see thermal radiation at the Hawking temperature. The positive specific heat of large AdS black holes is a statement about the dual gauge theory rather than an observable property on the gravity side. Implications for string thermodynamics with an AdS infrared regulator are briefly discussed

  19. Supersymmetric Kaluza-Klein reductions of AdS backgrounds

    Figueroa-O'Farrill, J M; Farrill, Jos\\'e Figueroa-O'; Sim\\'on, Joan

    2004-01-01

    This paper contains a classification of smooth Kaluza--Klein reductions (by one-parameter subgroups) of the maximally supersymmetric anti de Sitter backgrounds of supergravity theories. We present a classification of one-parameter subgroups of isometries of anti de Sitter spaces, discuss the causal properties of their orbits on these manifolds, and discuss their action on the space of Killing spinors. We analyse the problem of which quotients admit a spin structure. We then apply these results to write down the list of smooth everywhere spacelike supersymmetric quotients of AdS_3 x S^3 (x R^4), AdS_4 x S^7, AdS_5 x S^5 and AdS_7 x S^4, and the fraction of supersymmetry preserved by each quotient. The results are summarised in tables which should be useful on their own. The paper also includes a discussion of supersymmetry of singular quotients.

  20. Determination of insulin specific IgE in serum of diabetic patients by solid-phase radioimmunoassay

    A solid-phase assay system for quantitative measurement of insulin specific IgE has been developed. Insulin specific IgE and IgG are bound to insulin covalently coupled to Sepharose particles. After a washing procedure which removes unbound immunoglobulins, 125I-anti-human IgE-rabbit globulin is added to the Sepharose to determine the amount of bound IgE. The use of standardized 125I-anti-human-IgE-globulin permits quantitation against a calibration curve of IgE and expression as units/ml. No cross-reactivity of IgG was found. Insulin specific IgE was determined in the sera of diabetic patients. Patients treated with procine or mixed species purified insulin (monocomponent MC) did not differ significantly from a non-diabetic control group, whereas serum samples taken from patients treated with crystallized insulin preparations showed a significantly higher level of insulin specific IgE (p < 0.05). Twenty-four patients with generalized insulin allergy and eight patients with immunological insulin resistance also had considerably higher values of IgE antibodies than the control group (p < 0.001 and p < 0.005, respectively). No correlation was found between the concentration of insulin specific IgE and IgG in individual sera and the level of insulin specific IgE was independent of the total IgE. In all cases of allergy elicited by purified insulin (monocomponent MC), it was ascertained that the diabetic patients in question had received less pure insulin during earlier treatment. (orig.)

  1. ADS National Programmes: Netherlands

    The ADS related activities within the Netherlands are concentrated at NRG. From 2000 to 2006, NRG supported SCK•CEN in their development of MYRRHA. The support was mainly devoted to Computational Fluid Dynamics (CFD) simulations for the windowless target option. This collaboration was prolonged within the framework of the EU FP6 EUROTRANS project. Eventually this lead to a solution strategy for the hydraulic (without heat transfer) evaluation of a windowless target with one free surface using an Eulerian-Eulerian modeling approach. As a second free surface was added to the target design later, this approach would need to be revisited. The developed approach was applied to an assess the feasibility of a three feeder windowless target design. This preliminary assessment confirmed that there were no serious show stoppers for a three feeder design. Another study undertaken using related to the windowless target was a preliminary assessment of the risk of lead-bismuth splashing in case of a sudden heat deposition by the beam, e.g. at beam startup or beam interuptions. Within the framework of the EU FP7 CDT project, a window target is currently being assessed thermalhydraulicly in collaboration with SCK•CEN. Within the EU FP5 ASCHLIM project, the state of the art with regard to turbulence modelling for CFD approaches was determined. It was concluded that accurate simulation of heat transport in HLM was not feasible, especially in natural or mixed convection regimes. Within the EU FP7 THINS project this issue is currently being treated. NRG assists the commercial CFD code vendor CD adapco in implementing and testing a promising, academically tested, algebraic heat flux model

  2. Insulin delivery methods: Past, present and future.

    Shah, Rima B; Patel, Manhar; Maahs, David M; Shah, Viral N

    2016-01-01

    Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral hyperinsulinemia. Therefore, the need exists for delivering insulin in a minimally invasive or noninvasive and in most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver insulin, but it has been withdrawn from the market. Technologies are being explored to make the noninvasive delivery of insulin possible. Some of the routes of insulin administration that are under investigation are oral, buccal, nasal, peritoneal and transdermal. This review article focuses on the past, present and future of various insulin delivery techniques. This article has focused on different possible routes of insulin administration with its advantages and limitation and possible scope for the new drug development. PMID:27014614

  3. Chaos and hydrodynamics near AdS$_2$

    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.

  4. Minisuperspace limit of the AdS3 WZNW model

    Ribault, Sylvain

    2009-01-01

    We derive the three-point function of the AdS3 WZNW model in the minisuperspace limit by Wick rotation from the H3+ model. The result is expressed in terms of Clebsch-Gordan coefficients of the Lie algebra sl(2,R). We also introduce a covariant basis of functions on AdS3, which can be interpreted as bulk-boundary propagators.

  5. A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures

    Bonafede, Machaon MK; Kalsekar, Anupama; Pawaskar, Manjiri; Ruiz, Kimberly M; Torres, Amelito M; Kelly, Karen R.; Curkendall, Suellen M

    2010-01-01

    Objective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. Research design and methods: The Thomson Reuters MarketScan® databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-ba...

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

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

    1986-01-01

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

  7. Diabetes, insulin and cancer risk

    Xi-Lin Yang

    2012-01-01

    Full Text Available There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown. On the other hand, there are ongoing debates about the risk association of insulin use with cancer. We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer, as well as the current understanding of metabolic pathways implicated in intermediary metabolism and cellular growth. Based on the novel findings from the Hong Kong Diabetes Registry and consistent experimental evidence, we argue that use of insulin to control hyperglycemia is unlikely to contribute to increased cancer risk and that dysregulations in the AMP-activated protein kinase pathway due to reduced insulin action and insulin resistance, the insulin-like growth factor-1 (IGF-1-cholesterol synthesis pathway and renin-angiotensin system, presumably due to reduced insulin secretion and hyperglycemia, may play causal roles in the increased risk of cancer in diabetes. Further exploration into the possible causal relationships between abnormalities of these pathways and the risk of cancer in diabetes is warranted.

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

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

    2010-01-01

    Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4) patients with 1-24-year disease duration, in age group: 13-43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 10(3)/μL, CD45(-)/90(+)/73(+):40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1 × 10(3)/μL, CD45(-)/34(+):0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques. PMID:21197448

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

    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.

  10. Improved postprandial glycaemic control with insulin Aspart in type 2 diabetic patients treated with insulin

    Rosenfalck, A M; Thorsby, P; Kjems, L;

    2000-01-01

    The effect on postprandial blood glucose control of an immediately pre-meal injection of the rapid acting insulin analogue Aspart (IAsp) was compared with that of human insulin Actrapid injected immediately or 30 minutes before a test meal in insulin-treated type 2 diabetic patients with residual...... that the improved glucose control previously demonstrated with insulin Aspart compared to human insulin in healthy subjects and type 1 diabetic patients also applies to insulin-treated type 2 diabetic patients....

  11. Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice

    Wojtaszewski, Jørgen F. P.; Higaki, Yasuki; Hirshman, Michael F.; Michael, M. Dodson; Dufresne, Scott D.; Kahn, C. Ronald; Goodyear, Laurie J.

    1999-01-01

    Physical exercise promotes glucose uptake into skeletal muscle and makes the working muscles more sensitive to insulin. To understand the role of insulin receptor (IR) signaling in these responses, we studied the effects of exercise and insulin on skeletal muscle glucose metabolism and insulin signaling in mice lacking insulin receptors specifically in muscle. Muscle-specific insulin receptor knockout (MIRKO) mice had normal resting 2-deoxy-glucose (2DG) uptake in soleus muscles but had no si...

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

    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.

  13. Insulin in Central Nervous System: More than Just a Peripheral Hormone

    Ana I. Duarte

    2012-01-01

    Full Text Available Insulin signaling in central nervous system (CNS has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

  14. ADS National Programmes: Belarus

    The Belarus activities in the field of Accelerator Driven Systems (ADS) are mainly related to the investigations performed at the subcritical facility YALINA. Yalina is a zero power subcritical facility to study neutronics of ADS and the transmutation reaction rates. The first assembly YALINA-T was put into operation in 2000. YALINA-T is a multiplying system (kmax<0.98), located inside a graphite reflector of parallelepiped configuration that is arranged of high purity reactor graphite blocks. The core of the assembly is of parallelepiped configuration too and consists of bare polyethylene subassemblies where fuel rods of EK-10 type (UO2 of 10% enrichment by U235) are located. At the core center a neutron producing Pb target is located that reminds fuel subassembly by shape and size. Graphite reflector is covered from outside by Cd. At the distances R=50 mm, 100 mm, 150 mm from the core center three experimental channels (D=25 mm) are situated for location of samples of radioactive targets and various detectors for measurement of neutron flux density functionals. For the same purpose two axial channels (D=25 mm) are located in graphite reflector at the distances 250 mm and 358 mm; by Z=H/2 one more radial channel (D=25 mm) is located. YALINA-B core is arranged of rectangular parallelepipeds too. The fast (booster) zone consists of lead subassemblies, the thermal one of polyethylene subassemblies. Central part of the booster zone, containing highly enriched (90%) metallic uranium fuel and Pb target is encased into a separate stainless steel frame. The absorber zone is located at the outer boundary of the booster zone. It consists of inner layer of rods with metallic natural uranium fixed in lead blocks, as in the previous cases, and of an outer layer of rods filled by boron carbide powder, B4C. Boron carbide rods are located in the same lattice as the uranium fuel pins in the booster zone with pin pitch 16.00 mm. This absorber zone enables fast neutrons to

  15. Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

    Kida, Y; Nyomba, B L; Bogardus, C; Mott, D M

    1991-01-01

    Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resista...

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

    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...... 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...

  17. Discrimination in Online Ad Delivery

    Sweeney, Latanya

    2013-01-01

    A Google search for a person's name, such as "Trevon Jones", may yield a personalized ad for public records about Trevon that may be neutral, such as "Looking for Trevon Jones?", or may be suggestive of an arrest record, such as "Trevon Jones, Arrested?". This writing investigates the delivery of these kinds of ads by Google AdSense using a sample of racially associated names and finds statistically significant discrimination in ad delivery based on searches of 2184 racially associated person...

  18. Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.

    Mann, N P; Johnston, D I; Reeves, W G; Murphy, M A

    1983-01-01

    Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11...

  19. Complexity Growth for AdS Black Holes

    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.

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

    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.

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

    \\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...

  2. ADS National Programmes: Germany

    The German R&D programme for ADS development is related to the partitioning and transmutation of spent fuel. This programme is implemented mainly by the three national research centres belonging to the Helmholtz Association, i.e. Karlsruhe Institute of Technology (KIT), Forschungszentrum Jülich (FZJ) in cooperation with the Technical University of Aachen (RWTH Aachen) and the Helmholtz Zentrum Dresden Rossendorf (HZDR). The main purpose of this R&D programme is the prospect to manage the high level radioactive waste such as to reduce the burden on a final repository. P&T does not eliminate the need for a final repository whatever the strategy, but it allows the reduction of the radio-toxicity associated with radioactive waste, the increase of the repository capacity as a consequence of the reduction of masses to be stored and their associated residual heat load. Different fuel cycle scenarios to implement P&T can be envisaged. These scenarios have been evaluated to identify the impact of P&T on the characteristics, number and deployment pace of the installations of the fuel cycle (reprocessing, fuel fabrication, storage etc). Almost all activities conducted in the R&D programme are embedded in European and international projects and initiatives. In the following more details on the relevant components of the R&D programme are summarized

  3. Treatment of insulin resistance in uremia.

    Stefanović, V; Nesić, V; Stojimirović, B

    2003-02-01

    Insulin resistance is a characteristic feature of uremia. As long as the hyperinsulinemia adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the beta cell compensatory response declines, and relative, or absolute, insulin deficiency develops. At this point glucose intolerance and eventually frank type 2 diabetes occur. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Several studies have confirmed that hemodialysis (HD) treatment significantly improves insulin resistance. Both CAPD and CCPD are shown to improve insulin resistance in uremic patients. Comparing the effect of PD and HD treatment, it was found that the CCPD group has significantly higher insulin sensitivity than the HD group with the CAPD group similar to HD. Treatment of calcium and phosphate disturbances, including vitamin D therapy, significantly reduces insulin resistance in uremia. Treatment with recombinant human erythropoietin (EPO) is an efficient way to increase hematocrit, to reverse cardiovascular problems and to improve insulin sensitivity. Angiotensin-converting enzyme inhibitors have been shown to improve insulin resistance, hyperinsulinemia and glucose intolerance in uremic patients. Thiazolidinediones (TZDs), the new insulin-sensitizing drugs, provide the proof that pharmacologic treatment of insulin resistance can be of enormous clinical benefit. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms. PMID:12653342

  4. Human insulin: DNA technology's first drug.

    The, M J

    1989-11-01

    The history, biologic activity, and immunogenicity of human insulin are described. Recombinant human insulin first entered clinical trials in humans in 1980. At that time, the A and B chains of the insulin molecule were produced separately and then combined by chemical techniques. Since 1986, a different recombinant process has been used. The human genetic coding for proinsulin is inserted into Escherichia coli cells, which are then grown by fermentation to produce proinsulin. The connecting peptide is cleaved enzymatically from proinsulin to produce human insulin. Studies indicate that there are no important differences between pork insulin and human insulin in terms of therapeutic efficacy and disposition after intravenous administration. Recombinant human insulin has a faster onset of action and lower immunogenicity than pork or beef insulin. Diabetic patients may have an improvement in glucose concentrations when their therapy is switched from animal-source insulin to human insulin. Such a change usually requires a dosage adjustment, which must be determined by a physician. Pharmacists are responsible for educating patients concerning all insulin products and for preventing patients from interchanging insulin products. The availability of human insulin as the first pharmaceutical product manufactured through recombinant DNA technology, however, has had little effect on the pharmacist's role in the care of such patients. The production of human insulin through recombinant DNA technology represents an important advance in the treatment of patients with diabetes. PMID:2690608

  5. Identification of phageotope of rat liver insulin receptor

    Introduction: Insulin receptor; a kind of growth factors overexpressed on hepatocellular carcinoma (HCC) cells, mediated HCC cells proliferation. The present study is to looking for' the inhibitors of the insulin receptor to suppress minor growth or to getting potent ligands targeted to HCC via affinity selection of a cyclic phage random peptide library (C7C NEB) displayed on bacteriophage M13. Methods: 17.7u of rat insulin receptor(SIGMA) immobilized on a 60 x 15mm polystyrene plate(Becton Dickinson) by incubating overnight at 4 degree C. After blocking and washing of the receptor coated plates 2 x 1011 virons of C7C phage library were added to the plate and the dish was incubated 40min at room temperature. Washed the dish with TBST and collected the phages attacked to the insulin receptors immobilized on the dish with 0.2M glycine-HCl. Positive phage clones were amplified with 200 μl ER2738 in 20ml LB-Medium in a 250 ml Erlenmeyer flask. The IC 50 ratio of the selected clones compared to the phage library mixture binding to insulin receptors was determined with a set of phages in ELISA assay. DNA sequencing of 10 positive clones were performed after three rounds of biopanning and the amino acid sequences of the fused peptides were deduced. Results: The IC50 of a positive phage clone after three rounds of biopanning was 1.23 x 108 virions, and that of the phage library mixture was 2.16 x 1010 (The ratio of the IC50 is 1: 172.4). Six peptides have a common sequence XXSXGYX via DNA sequencing. Another four peptide sequences are not similar to the motif. Corresponding peptides TK1 was synthesized according to the common sequence and the selected peptide. The TK1 partly inhibited the insulin binding to insulin receptor in three times of detection. Conclusion: A synthesized peptide TK1 with a common sequence XXSXGYX, shows special affinity to insulin receptor, was obtained via affinity selected from the C7C peptide library. It could be a potent suppressing agent and

  6. Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes

    LIAO Zhi-hong; WENG Jian-ping; CHEN Ying-li; LI Fang-ping; YAN Xiang; LU Hai; YAN Li; ZHOU Zhi-guang; ZHU Da-long; JI Li-nong

    2008-01-01

    Background A new inhalable insulin aerosoI(Inh-Ins)was developed in China.The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes.Regular porcine insulin(RI)was used as a control.Methods This study is a prospective,randomized,open-label,parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks.HbA1c,fasting plasma glucose(FPG),the 1-hour-postprandial blood glucose(1hPBG)and the 2-hour-postprandial blood glucose(2hPBG)were measured.Events were monitored for adverse effects.Results After 12 weeks,the HbA1c decreased significantly from baseline in both treatment groups,with no significant difference between the two regimens.In the Inh-Ins group,FPG,both 1hPBG and 2hPBG significantly declined from baseline after the 8th-and 12th-weeks of treatment.The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI.After 12 weeks,the pulmonary carbon monoxide diffusing capacity(DLco)was significantly lower in Inh-Ins group than in the RI.The main side effects of Inh-Ins were coughing,excessive sputum,and hypoglycemia.Conclusions Inh-Ins was effective in decreasing HbA1c like the RI.It was better in lowering the FPG and the 1hPBG than the RI.Its main side effects were coughing,excessive sputum,and hypoglycemia.Also,Inh-Ins slightly impaired DLco.

  7. Patient self-monitoring of blood glucose and refinements of conventional insulin treatment.

    Tattersall, R; Gale, E

    1981-01-01

    The compelling evidence that blood glucose control will slow or prevent microvascular complications has stimulated research to find better ways of managing insulin-dependent diabetes. The excellent results obtained with "open loop" insulin infusion systems suggest that the relative failure of conventional treatment is the result of (1) a lack of appropriate feedback to the patient and (2) the use of insulin regimens which do not mimic physiologic insulinemia, particularly in the basal state. Doctors regard blood glucose measurements as an essential part of diabetic management and extension of this technology to patients has added a new dimension, particularly in the assessment of control. Nevertheless, home blood-glucose monitoring will not necessarily improve diabetic control; the best results have been obtained when it has been offered as part of a package deal which includes more investment of time and interest by patients and doctor together with joint discussions of problems and changes in treatment. The biggest problem with conventional twice daily insulin regimens is to sustain constant basal insulin levels during the night. Attempts to obtain fasting normoglycemia with an injection before supper often result in nocturnal hyperinsulinemia and hypoglycemia. This can usually be resolved by changing to a three times daily regimen with an extra injection of NPH insulin at bedtime. Three times daily insulin injections with feedback from home blood-glucose monitoring give as good blood glucose control as infusion systems and are cheaper and more acceptable to patients. PMID:7006390

  8. Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies.

    Andreani, Tatiana; Kiill, Charlene P; de Souza, Ana Luiza R; Fangueiro, Joana F; Fernandes, Lisete; Doktorovová, Slavomira; Santos, Dario L; Garcia, Maria L; Gremião, Maria Palmira D; Souto, Eliana B; Silva, Amélia M

    2014-11-01

    The present work aimed at studying the interaction between insulin and SiNP surfaced with mucoadhesive polymers (chitosan, sodium alginate or polyethylene glycol) and the evaluation of their biocompatibility with HepG2 and Caco-2 cell lines, which mimic in vivo the target of insulin-loaded nanoparticles upon oral administration. Thus, a systematic physicochemical study of the surface-modified insulin-silica nanoparticles (Ins-SiNP) using mucoadhesive polymers has been described. The surfacing of nanoparticle involved the coating of silica nanoparticles (SiNP) with different mucoadhesive polymers, to achieve high contact between the systems and the gut mucosa to enhance the oral insulin bioavailability. SiNP were prepared by a modified Stöber method at room temperature via hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Interaction between insulin and nanoparticles was assessed by differential scanning calorimetry (DSC), X-ray and Fourier-transform infrared (FTIR) studies. The high efficiency of nanoparticles' coating resulted in more stable system. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands which are characteristic of α-helix content. In general, all developed nanoparticles demonstrated high biocompatible, at the tested concentrations (50-500 μg/mL), revealing no or low toxicity in the two human cancer cell lines (HepG2 and Caco-2). In conclusion, the developed insulin-loaded SiNP surfaced with mucoadhesive polymers demonstrated its added value for oral administration of proteins. PMID:25466464

  9. Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

    Gjesing, Anette P; Ribel-Madsen, Rasmus; Harder, Marie N; Eiberg, Hans; Grarup, Niels; Jørgensen, Torben; Ekstrøm, Claus T; Pedersen, Oluf; Hansen, Torben

    2015-01-01

    closely related to fasting insulin with a genetic correlation of 0.85. The effects of 82 selected susceptibility single nucleotide polymorphisms on these insulin secretion indices supported our interpretation of the data and added insight into the biological differences between the examined traits......AIMS/HYPOTHESIS: We examined the extent to which surrogate measures of insulin release have shared genetic causes. METHODS: Genetic and phenotypic correlations were calculated in a family cohort (n = 315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma....... RESULTS: We found a notable difference between the phenotypic and genetic correlations for the traits, emphasising that the phenotypic correlation is an insufficient measure of the magnitude of shared genetic impact. In addition, we found that corrected insulin response, insulinogenic index and incAUC for...

  10. Insulin secretion: mechanisms of regulation

    Radosavljević Tatjana

    2004-01-01

    Full Text Available Regulation of insulin secretion Beta cells are unique endocrine cells. They respond positively, in terms of insulin secretion, not only to changes in the extracellular glucose concentration, but also to activators of the phospholipase C (cholecystokinin or acetylcholine, and to activators of adenylate cyclase (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide. Major messengers which mediate glucose action for insulin release are Ca2%, adenosine triphosphate (ATP and diacylglycerol (DAG. Major pathways of insulin release stimulation There are four major pathways involved in stimulation of insulin release. The first pathway is KATP channel-dependent pathway in which increased blood glucose concentrations and increased b-cell metabolism result in a change in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP-dependent K% channels, depolarization of b-cell membrane, in increased voltage-dependent L-type Ca2%channel activity. Increased Ca2% influx results in increased intracellular Ca2% and stimulated insulin release. KATP channel-independent pathway augments Ca2%-stimulated insulun secretion of KATP channel-dependent pathway. Major potentiation of release results from hormonal and peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase activity is stimulated by hormones such as vasoactive intestinal peptide (VIP, glucagon-like peptide-1 (GLP-1, and so on. These hormones, acting via G protein, stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate (cAMP and activation of protein kinase A (PKA. Increased activity of PKA results in potentiation of insulin secretion.

  11. AdS-Carroll Branes

    Clark, T E

    2016-01-01

    Coset methods are used to determine the action of a co-dimension one brane (domain wall) embedded in (d+1)-dimensional AdS space in the Carroll limit in which the speed of light goes to zero. The action is invariant under the non-linearly realized symmetries of the AdS-Carroll spacetime. The Nambu-Goldstone field exhibits a static spatial distribution for the brane with a time varying momentum density related to the brane's spatial shape as well as the AdS-C geometry. The AdS-C vector field dual theory is obtained.

  12. Insulin-regulated Srebp-1c and Pck1 mRNA expression in primary hepatocytes from zucker fatty but not lean rats is affected by feeding conditions.

    Yan Zhang

    Full Text Available Insulin regulates the transcription of genes for hepatic glucose and lipid metabolism. We hypothesized that this action may be impaired in hepatocytes from insulin resistant animals. Primary hepatocytes from insulin sensitive Zucker lean (ZL and insulin resistant Zucker fatty (ZF rats in ad libitum or after an overnight fasting were isolated, cultured and treated with insulin and other compounds for analysis of gene expression using real-time PCR. The mRNA levels of one insulin-induced (Srebp-1c and one insulin-suppressed (Pck1 genes in response to insulin, glucagon, and compactin treatments in hepatocytes from ad libitum ZL and ZF rats were analyzed. Additionally, the effects of insulin and T1317 on their levels in hepatocytes from ad libitum or fasted ZL or ZF rats were compared. The mRNA levels of Srebp-1c, Fas, and Scd1, but not that of Insr, Gck and Pck1, were higher in freshly isolated hepatocytes from ad libitum ZF than that from ZL rats. These patterns of Srebp-1c and Pck1 mRNA levels remained in primary hepatocyte cultured in vitro. Insulin's ability to regulate Srebp-1c and Pck1 expression was diminished in hepatocytes from ad libitum ZF, but not ZL rats. Glucagon or compactin suppressed Srebp-1c mRNA expression in lean, but not fatty hepatocytes. However, glucagon induced Pck1 mRNA expression similarly in hepatocytes from ad libitum ZL and ZF rats. Insulin caused the same dose-dependent increase of Akt phosphorylation in hepatocytes from ad libitum ZL and ZF rats. It synergized with T1317 to induce Srebp-1c, and suppressed Pck1 mRNA levels in hepatocytes from fasted, but not that from ad libitum ZF rats. We demonstrated that insulin was unable to regulate its downstream genes' mRNA expression in hepatocytes from ad libitum ZF rats. This impairment can be partially restored in hepatocytes from ZF rats after an overnight fasting, a phenomenon that deserves further investigation.

  13. Insulin resistance: β-arrestin development

    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.

  14. Insulin and insulin-like growth factor receptors and responses

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  15. PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

    Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a key role in degrading both Aβ and insulin and deficient in IDE function is associated with Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) pathology. However, little is known about the cellular and molecular regulation of IDE expression. Here we show IDE levels are markedly decreased in DM2 patients and positively correlated with the peroxisome proliferator-activated receptor γ (PPARγ) levels. Further studies show that PPARγ plays an important role in regulating IDE expression in rat primary neurons through binding to a functional peroxisome proliferator-response element (PPRE) in IDE promoter and promoting IDE gene transcription. Finally, we demonstrate that PPARγ participates in the insulin-induced IDE expression in neurons. These results suggest that PPARγ transcriptionally induces IDE expression which provides a novel mechanism for the use of PPARγ agonists in both DM2 and AD therapies.

  16. Logarithmic AdS waves and Zwei-Dreibein gravity

    We show that the parameter space of Zwei-Dreibein Gravity (ZDG) in AdS3 exhibits critical points, where massive graviton modes coincide with pure gauge modes and new ‘logarithmic’ modes appear, similar to what happens in New Massive Gravity. The existence of critical points is shown both at the linearized level, as well as by finding AdS wave solutions of the full non-linear theory, that behave as logarithmic modes towards the AdS boundary. In order to find these solutions explicitly, we give a reformulation of ZDG in terms of a single Dreibein, that involves an infinite number of derivatives. At the critical points, ZDG can be conjectured to be dual to a logarithmic conformal field theory with zero central charges, characterized by new anomalies whose conjectured values are calculated

  17. Asymptotically AdS spacetimes with a timelike Kasner singularity

    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.

  18. Null warped AdS in higher spin gravity

    Breunhoelder, Veronika; Grumiller, Daniel; Prohazka, Stefan

    2015-01-01

    We equip three-dimensional spin-3 gravity in the principal embedding with a new set of boundary conditions that we call "asymptotically null warped AdS". We find a chiral copy of the Polyakov-Bershadsky algebra as asymptotic symmetry algebra, reminiscent of the situation in topologically massive gravity with strict null warped AdS boundary conditions. We prove the invertibility of the map between zuvielbein and metric variables and construct a global gauge transformation to half of AdS spin-3 gravity in the diagonal embedding. This explains why the theory is chiral and why the Polyakov-Bershadsky algebra arises. We then introduce chemical potentials, derive the entropy, free energy, and the holographic response functions, and conclude with a discussion.

  19. Branes in the euclidean AdS3

    In this work we propose an exact microscopic description of maximally symmetric branes in a euclidean AdS3 background. As shown by Bachas and Petropoulos, the most important such branes are localized along a euclidean AdS2 is contained in AdS3. We provide explicit formulas for the coupling of closed strings to such branes (boundary states) and for the spectral density of open strings. The latter is computed in two different ways first in terms of the open string reflection amplitude and then also from the boundary states by world-sheet duality. This gives rise to an important Cardy type consistency check. All the results are compared in detail with the geometrical picture. We also discuss a second class of branes with spherical symmetry and finally comment on some implications for D-branes in a 2D back hole geometry. (author)

  20. New Massive Gravity and AdS4 Counterterms

    We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS4). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS4 Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS3 gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory.

  1. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    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.

  2. All AdS7 solutions of type II supergravity

    In M-theory, the only AdS7 supersymmetric solutions are AdS7×S4 and its orbifolds. In this paper, we find and classify new supersymmetric solutions of the type AdS7×M3 in type II supergravity. While in IIB none exist, in IIA with Romans mass (which does not lift to M-theory) there are many new ones. We use a pure spinor approach reminiscent of generalized complex geometry. Without the need for any Ansatz, the system determines uniquely the form of the metric and fluxes, up to solving a system of ODEs. Namely, the metric on M3 is that of an S2 fibered over an interval; this is consistent with the Sp(1) R-symmetry of the holographically dual (1,0) theory. By including D8 brane sources, one can numerically obtain regular solutions, where topologically M3≅S3

  3. Entanglement entropy for free scalar fields in AdS

    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.

  4. New massive gravity and AdS(4) counterterms.

    Jatkar, Dileep P; Sinha, Aninda

    2011-04-29

    We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS(4)). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS(4) Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS(3) gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory. PMID:21635026

  5. Towards integrability for AdS3/CFT2

    We review the recent progress towards applying worldsheet integrability techniques to the AdS3/CFT2 correspondence to find its all-loop S matrix and Bethe–Yang equations. We study in full detail the massive sector of AdS3×S3×T4 superstrings supported by pure Ramond–Ramond (RR) fluxes. The extension of this machinery to accommodate massless modes, to the AdS3×S3×S3×S1 pure-RR background and to backgrounds supported by mixed background fluxes is also reviewed. While the results discussed here were found elsewhere, our presentation sometimes deviates from the one found in the original literature in an effort to be pedagogical and self-contained. (topical review)

  6. Patient Perspectives on Biosimilar Insulin.

    Wilkins, Alasdair R; Venkat, Manu V; Brown, Adam S; Dong, Jessica P; Ran, Nina A; Hirsch, James S; Close, Kelly L

    2014-01-01

    Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would "definitely" or "likely" use a biosimilar insulin, while 17% reported that they were "unlikely" to use or would "definitely not use" such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors. PMID:24876533

  7. How to achieve a predictable basal insulin?

    Kurtzhals, P

    2005-09-01

    The development of insulin analogues over the last two decades have aimed at optimising the pharmacokinetic profile of subcutaneously injected insulin for therapeutic use in diabetes mellitus. Rapid acting analogues were successfully engineered and marketed in the late 1990's. In engineering long-acting analogues it has been a particular challenge to obtain action profiles that would be predictable from day to day in the same person. The most recent approach has been to acylate the insulin molecule with a fatty acid which provides the insulin molecule with a specific affinity for albumin. The first clinically available agent of this type is insulin detemir. Pharmacological studies have shown that reversible albumin binding will protract absorption following subcutaneous injection but still allow the insulin molecule to be recognised by the insulin receptor following dissociation from the carrier protein. Moreover, the molecular features of insulin detemir are attractive in that the molecule can be formulated as a neutral aqueous solution and does not precipitate after injection. Together with an important buffering mechanism effected by plasma albumin binding, this explains a highly significant reduction of within-subject variability of pharmacodynamic response observed in repeat isoglycaemic clamp studies where insulin detemir was compared to other basal insulin products. No safety considerations have been identified in using albumin as an insulin carrier to protract and buffer insulin action. In assessing the clinical attractiveness of insulin analogues, it is furthermore critically important to consider how the molecular modifications impact efficacy and safety. A number of pharmacological studies have shown that insulin detemir overall retains the molecular pharmacological properties of native human insulin, including a physiological balance between metabolic and mitogenic potencies. Taken together, insulin detemir provides an attractive novel approach for

  8. Insulin receptors in the mammary gland

    Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of 125I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less 125I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less 125I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands

  9. Logarithmic conformal field theories and AdS correspondence

    Khorrami, A. M. Ghezelbash. M.; Aghamohammadi, A

    1998-01-01

    We generalize the Maldacena correspondence to the logarithmic conformal field theories. We study the correspondence between field theories in (d+1)-dimensional AdS space and the d-dimensional logarithmic conformal field theories in the boundary of $AdS_{d+1}$. Using this correspondence, we get the n-point functions of the corresponding logarithmic conformal field theory in d-dimensions.

  10. Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus.

    Vaag, A.; Henriksen, J E; Madsbad, S; Holm, N; Beck-Nielsen, H.

    1995-01-01

    12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes ...

  11. 门冬胰岛素与生物合成人胰岛素治疗新诊断Ⅱ型糖尿病的对照研究%Comparative study on clinical therapeutic effect of insulin aspart and biosynthetic human insulin in the treatment of newly diagnosed type 2 diabetes

    陈中英

    2012-01-01

    Objective To compare the clinical efficacy between insulin aspart and biosynthetic human insulin in the treatment of newly diagnosed type 2 diabetes. Methods Ninety-six newly diagnosed type 2 diabetic patients were randomly divided into insulin aspart group (treatment group, n=48) and biosynthetic human insulin group (control group, n =48). The patients received subcutaneous injection of insulin aspart or biosynthetic human insulin before daily meals, and they were treated with insulin glargine at the bedtime. The blood sugar levels, incidence of hypo-glycemic episodes and the dosage of insulin were compared between the two groups. Results After administration of the drugs, the blood sugar levels were significantly reduced, and the blood sugar levels was lower in insulin aspart group than in the control group. The incidence of hypoglycemia in the treatment group was lower than in the control group, and the difference was statistically significant. The dosage of insulin showed no significant difference in the two groups. Conclusion Insulin aspart was better in the control of blood sugar levels and more effective in the treatment of patients with type 2 diabetes.%目的 比较门冬胰岛素与生物合成人胰岛素治疗新诊断Ⅱ型糖尿病的临床疗效.方法 将新诊断的96例Ⅱ型糖尿病患者随机均分为2组,分别为门冬胰岛素(治疗)组和生物合成人胰岛素(对照)组.患者分别在每日餐前给予皮下注射门冬胰岛素和生物合成人胰岛素,且均每晚定时皮下注射一次甘精胰岛素.比较2组患者血糖、低血糖事件、胰岛素用量的差异.结果 用药后2组餐前及餐后的血糖含量均明显降低,且门冬胰岛素组餐前、餐后血糖均低于生物合成人胰岛素组;门冬胰岛素组患者低血糖发生次数低于生物合成人胰岛素组,差异有统计学意义;但2组胰岛素用量无显著差异.结论 门冬胰岛素能够更好地控制Ⅱ型糖尿病的血糖,对Ⅱ

  12. AdS black holes as reflecting cavities

    We use the identification between null singularities of correlators in the bulk with time singularities in the boundary correlators to study the analytic structure of time-dependent thermal Green functions using the eikonal approximation for classical solutions in the AdS black hole background. We show that the location of singularities in complex time can be understood in terms of null rays bouncing on the boundaries and singularities of the eternal black hole, giving the picture of a 'reflecting cavity'. We can then extract the general analytic expression for the asymptotic values of the frequencies of quasinormal modes in large AdS black holes.

  13. AdS black holes as reflecting cavities

    Amado, Irene

    2008-01-01

    We use the identification between null singularities of correlators in the bulk with time singularities in the boundary correlators to study the analytic structure of time-dependent thermal Green functions using the eikonal approximation for classical solutions in the AdS black hole background. We show that the location of singularities in complex time can be understood in terms of null rays bouncing on the boundaries and singularities of the eternal black hole, giving the picture of a `reflecting cavity'. We can then extract the general analytic expression for the asymptotic values of the frequencies of quasinormal modes in large AdS black holes.

  14. Smoothed Transitions in Higher Spin AdS Gravity

    Banerjee, Shamik; Castro, Alejandra; 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 degen...

  15. Small black holes in global AdS spacetime

    Jokela, Niko; Vuorinen, Aleksi

    2015-01-01

    We study finite temperature correlation functions and quasinormal modes in a strongly coupled conformal field theory holographically dual to a small black hole in global Anti-de Sitter spacetime. Upon variation of the black hole radius, our results smoothly interpolate between known limits corresponding to large black holes and thermal AdS space, implying that a non-Hermitian eigenvalue problem gets continuously transitioned into a Hermitian one. This provides justification for the use of small black holes as regulators in studies of black hole formation in global AdS spacetime.

  16. Phases of Global AdS Black Holes

    Basu, Pallab; Subramanian, P N Bala

    2016-01-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ($AdS_4$) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  17. Phases of global AdS black holes

    Basu, Pallab; Krishnan, Chethan; Subramanian, P. N. Bala

    2016-06-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ( AdS 4) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  18. Branes in AdS and pp-wave spacetimes

    Skenderis, K; Skenderis, Kostas; Taylor, Marika

    2002-01-01

    We find half supersymmetric AdS-embeddings in AdS_5 x S^5 corresponding to all quarter BPS orthogonal intersections of D3-branes with Dp-branes. A particular case is the Karch-Randall embedding AdS_4 x S^2. We explicitly prove that these embeddings are supersymmetric by showing that the kappa symmetry projections are compatible with half of the target space Killing spinors and argue that all these cases lead to AdS/dCFT dualities involving a CFT with a defect. We also find an asymptotically AdS_4 x S^2 embedding that corresponds to a holographic RG-flow on the defect. We then consider the pp-wave limit of the supersymmetric AdS-embeddings and show how it leads to half supersymmetric D-brane embeddings in the pp-wave background. We systematically analyze D-brane embeddings in the pp-wave background along with their supersymmetry. We construct all supersymmetric D-branes wrapped along the light-cone using operators in the dual gauge theory: the open string states are constructed using defect fields. We also fin...

  19. Positivity of energy for asymptotically locally AdS spacetimes

    Cheng, M C N; Cheng, Miranda C.N.; Skenderis, Kostas

    2005-01-01

    We derive necessary conditions for the spinorial Witten-Nester energy to be well-defined for asymptotically locally AdS spacetimes. We find that the conformal boundary should admit a spinor satisfying certain differential conditions and in odd dimensions the boundary metric should be conformally Einstein. We show that these conditions are satisfied by asymptotically AdS spacetimes. The gravitational energy (obtained using the holographic stress energy tensor) and the spinorial energy are equal in even dimensions and differ by a bounded quantity related to the conformal anomaly in odd dimensions.

  20. Perturbative entanglement thermodynamics for AdS spacetime: renormalization

    Mishra, Rohit; Singh, Harvendra

    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. ...

  1. Mixed-symmetry fields in AdS(5), conformal fields, and AdS/CFT

    Metsaev, R R

    2014-01-01

    Mixed-symmetry arbitrary spin massive, massless, and self-dual massive fields in AdS(5) are studied. Light-cone gauge actions for such fields leading to decoupled equations of motion are constructed. Light-cone gauge formulation of mixed-symmetry anomalous conformal currents and shadows in 4d flat space is also developed. AdS/CFT correspondence for normalizable and non-normalizable modes of mixed-symmetry AdS fields and the respective boundary mixed-symmetry anomalous conformal currents and shadows is studied. We demonstrate that the light-cone gauge action for massive mixed-symmetry AdS field evaluated on solution of the Dirichlet problem amounts to the light-cone gauge 2-point vertex of mixed-symmetry anomalous shadow. Also we show that UV divergence of the action for mixed-symmetry massive AdS field with some particular value of mass parameter evaluated on the Dirichlet problem amounts to the action of long mixed-symmetry conformal field, while UV divergence of the action for mixed-symmetry massless AdS fi...

  2. Pursuit of a perfect insulin.

    Zaykov, Alexander N; Mayer, John P; DiMarchi, Richard D

    2016-06-01

    Insulin remains indispensable in the treatment of diabetes, but its use is hampered by its narrow therapeutic index. Although advances in peptide chemistry and recombinant DNA-based macromolecule synthesis have enabled the synthesis of structurally optimized insulin analogues, the growing epidemics of obesity and diabetes have emphasized the need for diabetes therapies that are more efficacious, safe and convenient. Accordingly, a broad set of drug candidates, targeting hyperglycaemia plus other disease abnormalities, is now progressing through the clinic. The development of an insulin therapy that is responsive to glucose concentration remains an ultimate goal, with initial prototypes now reaching the proof-of-concept stage. Simultaneously, the first alternatives to injectable delivery have progressed to registration. PMID:26988411

  3. Insulin poisoning with suicidal intent

    Abhay Gundgurthi

    2012-01-01

    Full Text Available We report a 27-year-old paramedical lady with no known comorbidities, who presented with rapid-onset coma with hypoglycemia (plasma glucose at admission was 35 mg/dL. Clinical alertness suspected and confirmed the diagnosis of exogenous insulin administration probably with suicidal intent. During the course of her ICU stay, she developed bradycardia and hypotension which required ionotropic support. She remained in coma for 90 hours. A total of 470 g of dextrose was infused until she regained consciousness. No other complications of insulin overdose were observed during her stay in the hospital. Recovery was complete without any residual neurological deficits. Insulin administration should be kept in differential diagnosis when any case presents with coma and hypoglycemia, especially in paramedical personnel.

  4. Microvascular Recruitment in Insulin Resistance

    Sjøberg, Kim Anker

    hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...... the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...

  5. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    DU, XUELIANG; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals...

  6. Increased skeletal muscle capillarization enhances insulin sensitivity

    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. S...

  7. Quantification of adipose tissue insulin sensitivity

    Søndergaard, Esben; Jensen, Michael D

    2016-01-01

    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...

  8. Quantification of adipose tissue insulin sensitivity.

    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. PMID:27073214

  9. Insulin Aspart (rDNA Origin) Injection

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... or itching over the whole body shortness of breath wheezing dizziness blurred vision fast heartbeat sweating weakness ...

  10. The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion

    Øzbay, Aygen; Møller, N; Juhl, C;

    2012-01-01

    pulsatile insulin secretion were not significantly affected by the drugs. CONCLUSION: In conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain...

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

    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.

  12. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

    Almind, K; Bjørbaek, C; Vestergaard, H;

    1993-01-01

    Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate g...

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

    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....

  14. High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity

    Havekes Louis M

    2010-03-01

    Full Text Available Abstract Background Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat on whole body energy metabolism and tissue specific insulin sensitivity. Methods C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet, for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5. Results Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle. Conclusion In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin

  15. Serum Insulin, Proinsulin and Proinsulin/Insulin Ratio in Type 2 Diabetic Patients: As an Index of β-Cell Function or Insulin Resistance

    Kim, Nan Hee; Kim, Dong Lim; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop

    2000-01-01

    Background Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. Methods We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also...

  16. Lipocalin-2 inhibits autophagy and induces insulin resistance in H9c2 cells.

    Chan, Yee Kwan; Sung, Hye Kyoung; Jahng, James Won Suk; Kim, Grace Ha Eun; Han, Meng; Sweeney, Gary

    2016-07-15

    Lipocalin-2 (Lcn2; also known as neutrophil gelatinase associated lipocalin, NGAL) levels are increased in obesity and diabetes and associate with insulin resistance. Correlations exist between Lcn2 levels and various forms or stages of heart failure. Insulin resistance and autophagy both play well-established roles in cardiomyopathy. However, little is known about the impact of Lcn2 on insulin signaling in cardiomyocytes. In this study, we treated H9c2 cells with recombinant Lcn2 for 1 h followed by dose- and time-dependent insulin treatment and found that Lcn2 attenuated insulin signaling assessed via phosphorylation of Akt and p70S6K. We used multiple assays to demonstrate that Lcn2 reduced autophagic flux. First, Lcn2 reduced pULK1 S555, increased pULK1 S757 and reduced LC3-II levels determined by Western blotting. We validated the use of DQ-BSA to assess autolysosomal protein degradation and this together with MagicRed cathepsin B assay indicated that Lcn2 reduced lysosomal degradative activity. Furthermore, we generated H9c2 cells stably expressing tandem fluorescent RFP/GFP-LC3 and this approach verified that Lcn2 decreased autophagic flux. We also created an autophagy-deficient H9c2 cell model by overexpressing a dominant-negative Atg5 mutant and found that reduced autophagy levels also induced insulin resistance. Adding rapamycin after Lcn2 could stimulate autophagy and recover insulin sensitivity. In conclusion, our study indicated that acute Lcn2 treatment caused insulin resistance and use of gain and loss of function approaches elucidated a causative link between autophagy inhibition and regulation of insulin sensitivity by Lcn2. PMID:27090568

  17. Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR).

    Li, Daliang; Chen, Shiuhwei; Bellomo, Elisa A; Tarasov, Andrei I; Kaut, Callan; Rutter, Guy A; Li, Wen-hong

    2011-12-27

    Current methods of monitoring insulin secretion lack the required spatial and temporal resolution to adequately map the dynamics of exocytosis of native insulin granules in intact cell populations in three dimensions. Exploiting the fact that insulin granules contain a high level of Zn(2+), and that Zn(2+) is coreleased with insulin during secretion, we have developed a fluorescent, cell surface-targeted zinc indicator for monitoring induced exocytotic release (ZIMIR). ZIMIR displayed a robust fluorescence enhancement on Zn(2+) chelation and bound Zn(2+) with high selectivity against Ca(2+) and Mg(2+). When added to cultured β cells or intact pancreatic islets at low micromolar concentrations, ZIMIR labeled cells rapidly, noninvasively, and stably, and it reliably reported changes in Zn(2+) concentration near the sites of granule fusion with high sensitivity that correlated well with membrane capacitance measurement. Fluorescence imaging of ZIMIR-labeled β cells followed the dynamics of exocytotic activity at subcellular resolution, even when using simple epifluorescence microscopy, and located the chief sites of insulin release to intercellular junctions. Moreover, ZIMIR imaging of intact rat islets revealed that Zn(2+)/insulin release occurred largely in small groups of adjacent β cells, with each forming a "secretory unit." Concurrent imaging of ZIMIR and Fura-2 showed that the amplitude of cytosolic Ca(2+) elevation did not necessarily correlate with insulin secretion activity, suggesting that events downstream of Ca(2+) signaling underlie the cell-cell heterogeneity in insulin release. In addition to studying stimulation-secretion coupling in cells with Zn(2+)-containing granules, ZIMIR may find applications in β-cell engineering and screening for molecules regulating insulin secretion on high-throughput platforms. PMID:22160693

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

    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.

  19. Synergistic Effect of Insulin on in vitro Development of Immature Bovine Oocytes

    Mojtaba Dashtizad

    2010-01-01

    Full Text Available Problem statement: Development of efficient culture system to support embryonic development would be valuable when quality of produced embryos was important. However, the rate of bovine embryo production in vitro was still lower than expected. Present study, including of three experiments, was carried out to investigate the effect of insulin on nuclear maturation and subsequent development of immature bovine oocytes and in vitro fertilized embryos. Approach: Grade one cumulus-oocyte-complexes harvested from slaughterhouse ovaries were selected and randomly allocated in each treatment groups. In experiment 1, in vitro maturation medium (Hepes-buffered medium 199 + fetal calf serum + gonadotrophins + antibiotics supplemented with 0 (control, 1, 10, 20 and 100 µg mL-1 of insulin. In experiment 2, to eliminate the effect of serum and hormones, Hepesbuffered medium 199 was supplemented with 1 mg mL-1 polyvinyl alcohols (PVA and same levels of insulin. In experiment 3, the effect of insulin on bovine in vitro embryo development was assessed. Presumptive zygotes were randomly cultured in synthetic oviductal fluid added with 0 (control, 1, 10, 20 and 100 ìg mL-1 of insulin. Results: In experiment 1, nuclear maturation and embryo development rates were significantly higher in 1 and 10 µg mL-1 compared with other groups (P-1 insulin. The only treatment resulted in higher hatchability was 10 ìg mL-1 insulin (17.1±2.34% compared with control (11.34±3.94. In experiment 3, cleavage and morula rates were significantly greater in 1 and 10 µg mL-1 insulin compared with other groups; although the highest rates resulted by using 10 µg mL-1. Conclusion: Obtained results show that inclusion of 10 µg mL-1 insulin in maturation and culture medium exerted beneficial effects on nuclear maturation of bovine oocytes and in vitro embryo development till morula stage.

  20. Insulin Pump Safety Meeting: Summary Report

    Klonoff, David C; Reyes, Juliet S.

    2009-01-01

    Diabetes Technology Society convened a panel of insulin pump experts in Bethesda, Maryland, on November 12, 2008, at the request of the Food and Drug Administration. The group consisted of physicians, nurses, diabetes educators, and engineers from across the United States. The panel members (1) discussed safety features of insulin pump therapy and (2) recommended adjustments to current insulin pump design and use to enhance overall safety. Software and hardware features of insulin pumps were ...

  1. Role of Mitochondrial Dysfunction in Insulin Resistance

    Kim, Jeong-a; Wei, Yongzhong; Sowers, James R.

    2008-01-01

    Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the patho...

  2. Safety and Efficacy of Modern Insulin Analogues

    Hye Jin Yoo; Keun Yong Park; Kang Seo Park; Kyu Jeung Ahn; Kyung Wan Min; Jeong Hyun Park; Sang Ah Chang; Bong Soo Cha; Dong-Jun Kim; Yong Seong Kim; Tae Keun Oh; Suk Chon; Il Seong Nam-Goong; Mi Jin Kim; Hye-Soon Kim

    2013-01-01

    Background A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. Methods Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at base...

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

    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.

  4. AdS (instability: Lessons from the scalar field

    Pallab Basu

    2015-06-01

    Full Text Available We argued in arXiv:1408.0624 that the quartic scalar field in AdS has features that could be instructive for answering the gravitational stability question of AdS. Indeed, the conserved charges identified there have recently been observed in the full gravity theory as well. In this paper, we continue our investigation of the scalar field in AdS and provide evidence that in the Two-Time Formalism (TTF, even for initial conditions that are far from quasi-periodicity, the energy in the higher modes at late times is exponentially suppressed in the mode number. Based on this and some related observations, we argue that there is no thermalization in the scalar TTF model within time-scales that go as ∼1/ϵ2, where ϵ measures the initial amplitude (with only low-lying modes excited. It is tempting to speculate that the result holds also for AdS collapse.

  5. Penrose inequality for asymptotically AdS spaces

    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.

  6. BRST Quantization of String Theory in AdS(3)

    Pakman, A

    2003-01-01

    We study the BRST quantization of bosonic and NSR strings propagating in AdS(3) x N backgrounds. The no-ghost theorem is proved using the Frenkel-Garland-Zuckerman method. Regular and spectrally-flowed representations of affine SL(2,R) appear on an equal footing. Possible generalizations to related curved backgrounds are discussed.

  7. Internet Advertising. Google AdWords versus Facebook Ads

    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.

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

    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.

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

    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.

  10. Thermal dissociation and unfolding of insulin

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

    2005-01-01

    The thermal stability of human insulin was studied by differential scanning microcalorimetry and near-UV circular dichroism as a function of zinc/protein ratio, to elucidate the dissociation and unfolding processes of insulin in different association states. Zinc-free insulin, which is primarily...

  11. Insulin sensitivity : modulation by the brain

    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

  12. Bioavailability and variability of biphasic insulin mixtures

    Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik; Colding-Jørgensen, Morten

    2012-01-01

    insulin degradation. Soluble insulins are assumed to be degraded enzymatically in the subcutaneous tissue. Suspended insulin crystals form condensed heaps that are assumed to be degraded from their surface by invading macrophages. It is demonstrated how the shape of the heaps affects the absorption...

  13. Entanglement temperature and perturbed AdS3 geometry

    Levine, G. C.; Caravan, B.

    2016-06-01

    Generalizing the first law of thermodynamics, the increase in entropy density δ S (x ) of a conformal field theory (CFT) is proportional to the increase in energy density, δ E (x ) , of a subsystem divided by a spatially dependent entanglement temperature, TE(x ) , a fixed parameter determined by the geometry of the subsystem, crossing over to thermodynamic temperature at high temperatures. In this paper we derive a generalization of the thermodynamic Clausius relation, showing that deformations of the CFT by marginal operators are associated with spatial temperature variations, δ TE(x ) , and spatial energy correlations play the role of specific heat. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature of the CFT and the perturbation of the bulk AdS metric. In two dimensions, we demonstrate a method through which direct diagonalizations of the boundary quantum theory may be used to construct geometric perturbations of AdS3 .

  14. AdS5 backgrounds with 24 supersymmetries

    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.

  15. AdS5 Backgrounds with 24 Supersymmetries

    Beck, S W; Papadopoulos, G

    2016-01-01

    We prove a non-existence theorem for smooth AdS5 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 strictly N=3 superconformal theories in 4-dimensions exist, their gravitational dual backgrounds are either singular or their internal spaces are not compact.

  16. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    Castillo, C.; Bogardus, C; Bergman, R.; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  17. Clinical application of insulin pumps in the management of insulin dependent diabetes.

    Greene, S.A.; Smith, M. A.; Baum, J D

    1983-01-01

    Seven volunteers aged 12.0 to 17.9 years participated in a trial to compare conventional insulin treatment with continuous open loop (pump) insulin infusion. After 6 weeks of conventional treatment followed by 6 weeks of insulin pump treatment, 4 children chose to manage their diabetes permanently by means of the insulin pump. The mean blood glucose concentration (based on home blood glucose monitoring) while on conventional insulin treatment showed no appreciable change during the 6 weeks' t...

  18. Subetta increases phosphorylation of insulin receptor β-subunit alone and in the presence of insulin

    Gorbunov, E A; Nicoll, J; Kachaeva, E. V.; Tarasov, S A; Epstein, O. I.

    2015-01-01

    It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor β-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or pre...

  19. Insulin signal transduction in skeletal muscle : special consideration for insulin resistance and diabetes

    Song, Xiao Mei

    2000-01-01

    This dissertation work is focused on the insulin-signal-transduction pathways to glucose transport in skeletal muscle from animal models of NIDDM. The overall objective is to determine the effectiveness of different pharmacological treatments to improve insulin action in skeletal muscle. Muscle-fiber-type-specific differences in insulin signal transduction was first considered. We noted increased insulin action on insulin signaling events including; IR, IRS- 1, IRS-2, PI...

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

    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

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

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

    2016-08-01

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

  2. Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes.

    Manowsky, Julia; Camargo, Rodolfo Gonzalez; Kipp, Anna P; Henkel, Janin; Püschel, Gerhard P

    2016-06-01

    Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. PMID:27094035

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

    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....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

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

    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.

  5. The PredictAD project

    Antila, Kari; Lötjönen, Jyrki; Thurfjell, Lennart;

    2013-01-01

    objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data...

  6. Nutritional Modulation of Insulin Resistance

    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.

  7. Mitochondrial efficiency and insulin resistance.

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2014-01-01

    Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle. PMID:25601841

  8. Self-dual warped AdS3 black holes

    Chen, Bin; Ning, Bo

    2010-12-01

    We study a new class of solutions of three-dimensional topological massive gravity. These solutions can be taken as nonextremal black holes, with their extremal counterparts being discrete quotients of spacelike warped AdS3 along the U(1)L isometry. We study the thermodynamics of these black holes and show that the first law is satisfied. We also show that for consistent boundary conditions, the asymptotic symmetry generators form only one copy of the Virasoro algebra with central charge cL=(4νℓ)/(G(ν2+3)), with which the Cardy formula reproduces the black hole entropy. We compute the real-time correlators of scalar perturbations and find a perfect match with the dual conformal field theory (CFT) predictions. Our study provides a novel example of warped AdS/CFT correspondence: the self-dual warped AdS3 black hole is dual to a CFT with nonvanishing left central charge. Moreover, our investigation suggests that the quantum topological massive gravity asymptotic to the same spacelike warped AdS3 in different consistent ways may be dual to different two-dimensional CFTs.

  9. String theory in AdS3 background

    In this thesis we study string theory in AdS3 background in the context of AdS/CFT correspondence. We discuss unitarity, modular invariance and closure of operator product expansion (OPE) in the theory. A construction of spacetime conformal field theory from worldsheet affine symmetry due to Giveon, Kutasov and Seiberg is presented. The spacetime CFT has the meaning boundary CFT in AdS/CFT correspondence. The knowledge of two dimensional N extended superconformal algebras is used to construct superstrings on AdS3 x N with extended spacetime supersymmetry. A classification of vacua of superstrings on AdS3 is proposed from the knowledge of superconformal algebras in two dimensions. We present some exact solutions of Kniznik-Zamolodochikov (KZ) equation for SL(2, R) WZNW model for four point functions, which have logarithmic singularities of conformally invariant cross ratios, from a simple ansatz. Some asymptotic solutions with logarithmic behaviour are also presented. We analyze the logarithmic solutions and show that they can give rise to logarithmic operators in the theory. It has been shown by OPE analysis and otherwise that representation with SL(2, R) quantum number j = -1/2 play a very special role. The possibility of contribution oj logarithmic operators to the OPE is discussed. We find that OPE can not close or unitary representations if we include the logarithmic operators in the theory. We discuss the implications of logarithmic operators about the unitarity of the theory. The role of singleton representation is clarified in the context of logarithmic operators in AdS/CFT correspondence. (author)

  10. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

    Jon B Toledo

    Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

  11. Lipoic acid improves neuronal insulin signalling and rescues cognitive function regulating VGlut1 expression in high-fat-fed rats: Implications for Alzheimer's disease.

    Rodriguez-Perdigon, Manuel; Solas, Maite; Moreno-Aliaga, Maria Jesús; Ramirez, Maria Javier

    2016-04-01

    The concept of central insulin resistance and dysfunctional insulin signalling in sporadic Alzheimer's disease (AD) is now widely accepted and diabetes is recognized as one of the main risk factors for developing AD. Moreover, some lines of evidence indicated that VGlut1 is impaired in frontal regions of AD patients and this impairment is correlated with the progression of cognitive decline in AD. The present work hypothesizes that ketosis associated to insulin resistance could interfere with the normal activity of VGlut1 and its role in the release of glutamate in the hippocampus, which might ultimately lead to cognitive deficits. High fat diet (HFD) rats showed memory impairments and both peripheral (as shown by increased fasting plasma insulin levels and HOMA index) and hippocampal (as shown by decreased activation of insulin receptor, IRS-1 and pAkt) insulin pathway alterations, accompanied by increased ketone bodies production. All these effects were counteracted by α-lipoic acid (LA) administration. VGlut1 levels were significantly decreased in the hippocampus of HFD rats, and this decrease was reversed by LA. Altogether, the present results suggest that HFD induced alterations in central insulin signalling could switch metabolism to produce ketone bodies, which in turn, in the hippocampus, might lead to a decreased expression of VGlut1, and therefore to a decreased release of glutamate and hence, to the glutamatergic deficit described in AD. The ability of LA treatment to prevent the alterations in insulin signalling in this model of HFD might represent a possible new therapeutic target for the treatment of AD. PMID:26769360

  12. Leptin therapy, insulin sensitivity, and glucose homeostasis

    Gilberto Paz-Filho

    2012-01-01

    Full Text Available Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insulinemia and insulin resistance. The understanding of the effects of leptin on the glucose-insulin homeostasis will lead to the development of leptin-based therapies against diabetes and other insulin resistance syndromes. In these review, we summarize the interactions between leptin and insulin, and their effects on the glucose metabolism.

  13. Pathogenesis of Insulin Resistance in Skeletal Muscle

    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.

  14. Effect of fructose on insulin action in adipose tissue of Wistar rats

    The present study was conducted to examine the effects of dietary fructose, with and without insulin stimulation, on glucose oxidation to carbon dioxide and on fatty acid synthesis in epididymal adipose tissue of rats. Two groups of male weanling Wistar rats were fed ad libitum 54% (W/W) carbohydrate diets containing 27% cornstarch plus either 27% D-fructose (FRU) or 27% D-glucose (GLU) for eleven weeks. Each diet also contained 16% fat and 20% protein. Neither body weights nor epididymal adipose tissue weights were significantly different between groups. Insulin action was assessed by incubating adipose tissue in Krebs-Ringer bicarbonate buffer (pH 7.4) containing 90 μmoles [U-14C]-D-glucose with and without insulin (1 mU/ml) for 1 hour, trapping the 14CO2 on filter paper, and extracting the 14C-lipid with Dole's mixture. Means +/- SEM with identical superscripts are not different at the P < .05 level. These results indicate that FRU feeding stimulated glucose oxidation at a rate higher than that of GLU feeding and comparable to that stimulated by insulin. However, lipogenesis was lower in FRU fed than either in GLU fed rats or with insulin stimulation. FRU feeding does not alter the action of insulin on glucose oxidation or lipogenesis

  15. Brain Insulin Signaling Is Increased in Insulin-Resistant States and Decreases in FOXOs and PGC-1α and Increases in Aβ1-40/42 and Phospho-Tau May Abet Alzheimer Development.

    Sajan, Mini; Hansen, Barbara; Ivey, Robert; Sajan, Joshua; Ari, Csilla; Song, Shijie; Braun, Ursula; Leitges, Michael; Farese-Higgs, Margaret; Farese, Robert V

    2016-07-01

    Increased coexistence of Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) suggests that insulin resistance abets neurodegenerative processes, but linkage mechanisms are obscure. Here, we examined insulin signaling factors in brains of insulin-resistant high-fat-fed mice, ob/ob mice, mice with genetically impaired muscle glucose transport, and monkeys with diet-dependent long-standing obesity/T2DM. In each model, the resting/basal activities of insulin-regulated brain protein kinases, Akt and atypical protein kinase C (aPKC), were maximally increased. Moreover, Akt hyperactivation was accompanied by hyperphosphorylation of substrates glycogen synthase kinase-3β and mammalian target of rapamycin and FOXO proteins FOXO1, FOXO3A, and FOXO4 and decreased peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression. Akt hyperactivation was confirmed in individual neurons of anterocortical and hippocampal regions that house cognition/memory centers. Remarkably, β-amyloid (Aβ1-40/42) peptide levels were as follows: increased in the short term by insulin in normal mice, increased basally in insulin-resistant mice and monkeys, and accompanied by diminished amyloid precursor protein in monkeys. Phosphorylated tau levels were increased in ob/ob mice and T2DM monkeys. Importantly, with correction of hyperinsulinemia by inhibition of hepatic aPKC and improvement in systemic insulin resistance, brain insulin signaling normalized. As FOXOs and PGC-1α are essential for memory and long-term neuronal function and regeneration and as Aβ1-40/42 and phospho-tau may increase interneuronal plaques and intraneuronal tangles, presently observed aberrations in hyperinsulinemic states may participate in linking insulin resistance to AD. PMID:26895791

  16. Observing quantum gravity in asymptotically AdS space

    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.

  17. Smoothed transitions in higher spin AdS gravity

    We consider CFTs conjectured to be dual to higher spin theories of gravity in AdS3 and AdS4. Two-dimensional CFTs with WN symmetry are considered in the λ = 0 (k → ∞) 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 1; 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 T3, 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 a large level k. (paper)

  18. AdS nonlinear instability: moving beyond spherical symmetry

    Dias, Oscar J C

    2016-01-01

    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 [1,2]. We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied in [2]. In contrast with [2], 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 in [2]. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of [2]. 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.

  19. Ambitwistors, oscillators and massless fields on $AdS_5$

    Uvarov, D V

    2016-01-01

    Positive energy unitary irreducible representations of $SU(2,2)$ can be constructed with the aid of bosonic oscillators in (anti)fundamental representation of $SU(2)_L\\times SU(2)_R$ that are closely related to Penrose twistors. Starting with the correspondence between the doubleton representations, homogeneous functions on projective twistor space and on-shell $SL(2,\\mathbb C)$ generalized Weyl curvature spinors and their low-spin counterparts, we study in the similar way the correspondence between the massless representations, homogeneous functions on ambitwistor space and, via the Penrose transform, with the gauge fields on Minkowski boundary of $AdS_5$. The possibilities of reconstructing massless fields on $AdS_5$ and some applications are also discussed.

  20. The Mixed Phase of Charged AdS Black Holes

    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.