-247--59-atropine-pmoll--min-P--0001-o

More glucose was needed to maintain the clamp during the high-dose GLP-1 infusion steady-state period on the atropine day [6 ± 0 (saline) vs. 8 ± 0 (atropine) mg·kg(-1)·min(-1), P < 0023]. GLP-1 dose-dependently increased insulin secretion on both days. The insulinotropic effect of GLP-1 was not impaired by atropine [C-peptide AUCs45-145: 99 ± 8 (saline) vs. 113 ± 13 (atropine) nmol/l × min, P = 09]. Atropine suppressed glucagon levels additively with GLP-1 [AUC45-145: 469 ± 70 (saline) vs.

265 ± 50 (atropine) pmol/l × min, P = 018], resulting in hypoglycemia when infusions were suspended [3 ± 0 (saline) vs. 2 ± 0 (atropine) mmol/l, P < 0001]. To ascertain whether atropine could independently suppress glucagon levels, control experiments (n = 5) were carried out without GLP-1 infusions [AUC45-145: 558 ± 103 (saline) vs. 382 ± 76 (atropine) pmol/l × min, P = 06]. Our results suggest that efferent muscarinic activity is not required for the insulinotropic effect of exogenous GLP-1 but that blocking efferent muscarinic activity independently suppresses glucagon secretion. In combination, GLP-1 and muscarinic blockade strongly affect glucose turnover.Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials.

BACKGROUND: The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. glucagon-like peptide-1 drugs of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients.METHODS: PubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.RESULTS: We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 00; 95% CI: 03-07; P = 004) and fatal or non-fatal stroke (RR: 05; 95% CI: 07-04; P = 001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 01; 95% CI: 02 - 11; CONCLUSION: We concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular Conflict of interest statement: All authors declare that there are no conflict of interests or special relationships with industry in this meta-analysis.

GLP‑1 receptor agonist protects palmitate-induced insulin resistance in skeletal muscle cells by up-regulating sestrin2 to promote autophagy.In this study, we aimed to determine whether liraglutide could effectively reduce insulin resistance (IR) by regulating Sestrin2 (SESN2) expression in L6 rat skeletal muscle cells by examining its interactions with SESN2, autophagy, and IR. L6 cells were incubated with liraglutide (10-1000 nM) in the presence of palmitate (PA; 0 mM), and cell viability was detected using the cell counting kit-8 (CCK-8) assay. IR-related and autophagy-related proteins were detected using western blotting, and IR and autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction. Silencing SESN2 was used to inhibit the activities of SESN2. A reduction in insulin-stimulated glucose uptake was observed in PA-treated L6 cells, confirming IR. Meanwhile, PA decreased the levels of GLUT4 and phosphorylation of Akt and affected SESN2 expression.

Further investigation revealed that autophagic activity decreased following PA treatment, but that liraglutide reversed this PA-induced reduction in autophagic activity. Additionally, silencing SESN2 inhibited the ability of liraglutide to up-regulate the expression of IR-related proteins and activate autophagy signals. In summary, the data showed that liraglutide improved PA-induced IR in L6 myotubes by increasing autophagy mediated by SESN2.Conflict of interest statement: The authors declare no competing interests.Glucagon-like peptide-1 (GLP-1): a trial of treatment in non-insulin-dependent Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In API Hormones and Regulation to presently available therapeutic agents for non-insulin-dependent diabetes mellitus (NIDDM), GLP-1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. We report the first chronic study of subcutaneous (s/c) GLP-1 treatment in NIDDM.

Five patients with poorly controlled NIDDM were entered into a six-week, double-blind crossover trial. Each received three weeks treatment with s/c GLP-1 40 nmol or saline, given three times a day immediately before meals.