Notes

In this review, we summarize the current knowledge regarding the role of GLP-1 in the protection against oxidative damage and the activation of the Nrf2 signaling pathway
Conflict of interest statement: The authors declare no conflict of interest.Effect of glucagon-like peptide-1 gene expression on graft function in mouse This study investigated the effect of local glucagon-like peptide-1 (GLP-1) production within mouse islets on cytoprotection in vitro and in vivo by gene transfer of GLP-1. Transduction of recombinant adenovirus vector expressing GLP-1 (rAd-GLP-1) induced a significant increase in bioactive GLP-1 in the mouse islet culture, whereas transduction with adenovirus vector expressing β-galactosidase (rAd-LacZ), as a control, had no effect on GLP-1 secretion. damage in vitro. In Pancreatic hormones and other blood sugar regulating drugs , glucose-stimulated insulin secretion was significantly increased in rAd-GLP-1-transduced islets. When transplanted under the kidney capsule of diabetic syngeneic mice, islet grafts retrieved 4 or 7 days after transplantation revealed that the rAd-GLP-1-transduced group had significantly more Ki67-positive cells as compared with the rAd-LacZ-transduced group.

Regarding blood glucose control, diabetic mice transplanted with a marginal mass of rAd-GLP-1-transduced islets became normoglycemic more rapidly and 78% of the recipients were normoglycemic at 35 days post-transplant, whereas only 48% of the mice transplanted with rAd-LacZ-transduced islets were normoglycemic (P < 05). In conclusion, delivery of the GLP-1 gene to islets enhanced islet cell survival during the early post-transplant period, and preserved islet mass and functions over time in the transplants.Glucagon and GLP-1 inhibit food intake and increase c-fos expression in similar appetite regulating centres in the brainstem and amygdala.BACKGROUND: Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. glucagon-like peptide 1 of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied.

Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies.OBJECTIVES: To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination.METHODOLOGY: Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and RESULTS: Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone.CONCLUSION: Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression.

Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.Protease-resistant glucagon like peptide-1 analogs with long-term anti-diabetes agonist, has been developed by GlaxoSmithKline for the treatment of type 2 diabetes mellitus (T2DM). Albiglutide has received its first global approval in this indication in the EU, for use in combination with other antihyperglycaemic agents, including basal insulin, when these drugs and diet and exercise do not provide adequate glycaemic control, and as monotherapy in patients unable to take metformin due to contraindications or intolerance when diet and exercise alone do not provide adequate glycaemic control. Albiglutide has subsequently been approved for the second-line or later treatment of T2DM as an adjunct to diet and exercise in the US. This article summarizes the milestones in the development of albiglutide leading to this first approval for the treatment of 10016/j.diabres017217.

Epub 2017 Feb 20.Albiglutide for the treatment of type 2 diabetes mellitus: An integrated safety analysis of the HARMONY phase 3 trials.Clinical Statistics, Research Triangle Park, Durham, NC, USA. Electronic AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM.METHODS: Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione).
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