Glucagon-like peptide-1 increased the vascular relaxation response via AMPK/Akt signaling in diabetic mice aortas.

This study aimed to evaluate the acute effects of GLP-1 on improving aortic endothelial dysfunction in diabetic mice. Additionally, we examined whether GLP-1 elucidated the underlying mechanisms. Using the diabetic mouse models induced by nicotinamide and streptozotocin, we investigated the functional changes in the aorta caused by GLP-1. Organ baths were performed for vascular reactivity in isolated aortic rings, and western blotting was used for protein analysis. The diabetic aortas showed enhanced GLP-1-induced relaxation response and nitric oxide (NO) production. However, the pretreatment of GLP-1 did not significantly change the endothelial-dependent relaxation response to acetylcholine and -independent relaxation response to sodium nitroprusside. On the other hand, the GLP-1-induced relaxation response and NO production were abolished by the endothelial NO synthase inhibitor, GLP-1 receptor antagonist, Akt inhibitor, and AMP-activated protein kinase (AMPK) inhibitor. Finally, in diabetic mice, considerable increases in phosphorylation of Akt and AMPK were found in aortas stimulated with GLP-1, both of which were decreased by pretreatment with the AMPK inhibitor. GLP-1 significantly enhanced endothelial-dependent relaxation in diabetic aortas. The effect may be mediated through activation of the AMPK/Akt pathway via a GLP-1 receptor-dependent mechanism. PMID: 31697935 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research

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ConclusionsRepeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.
Source: Journal of Endocrinological Investigation - Category: Endocrinology Source Type: research
Purpose of review Incretin-based therapies mimic or augment the gut-hormone glucagon-like peptide (GLP)-1 and, due to their glucose-lowering potential and beneficial safety profile, as well as their cardiovascular safety and/or protection, are prescribed on a large scale to treat individuals with type 2 diabetes (T2D). However, whether the two drug-classes that belong to this category, respectively GLP-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, also reduce the risk of diabetic kidney disease (DKD) is at present heavily debated. This review aims to discuss the current evidence. Recent findings Evi...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: HORMONES, AUTACOIDS, NEUROTRANSMITTERS AND GROWTH FACTORS: Edited by Mark Cooper and Merlin Thomas Source Type: research
Incretin-based glucose-lowering medications (glucagon-like peptide-1 receptor agonists, GLP-1 RAs, and inhibitors of dipeptidyl peptidase-4, DPP-4 I) are now established drug classes, widely used because of their ability to substantially reduce high plasma glucose concentrations and levels of glycated hemoglobin without themselves causing hypoglycemic episodes, doing so without prompting body weight gain (DPP-4-I) or even with a chance to meaningfully reduce adipose tissue mass (GLP-1 RA) [1, 2].
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
Condition:   Type 1 Diabetes Mellitus Interventions:   Drug: Metformin;   Drug: Placebo Sponsor:   Hellenic Institute for the Study of Sepsis Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 20 November 2019Source: PeptidesAuthor(s): Sravan K. Thondam, Daniel J. Cuthbertson, John P.H. WildingAbstractGlucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) are the two incretin hormones secreted by the enteroendocrine system in response to nutrient ingestion. Compared with GLP-1, GIP is less well studied as a hormone or as a potential pharmacological treatment. Beyond its insulinotropic effects in the pancreas, GIP has important biological actions in many other tissues but its role in dietary fat metabolism and lipid storage in adipose tissue has bee...
Source: Peptides - Category: Biochemistry Source Type: research
Publication date: Available online 19 November 2019Source: PeptidesAuthor(s): Clifford J. BaileyAbstractThe potential application of glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide, GIP) in the management of obesity and type 2 diabetes has been controversial. Initial interest in the therapeutic use of GIP was dampened by evidence that its insulinotropic activity was reduced in type 2 diabetes and by reports that it increased glucagon secretion and adipose deposition in non-diabetic individuals. Also, attention was diverted away from GIP by the successful development of glucagon-like peptide-1 (...
Source: Peptides - Category: Biochemistry Source Type: research
Publication date: Available online 18 November 2019Source: PeptidesAuthor(s): Rabeet Khan, Alejandra Tomas, Guy A. RutterAbstractGlucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin that, in common with glucagon-like peptide-1 (GLP-1), has both insulin releasing and extra-pancreatic glucoregulatory actions. GIP is released in response to glucose or fat absorption and acts on the GIP receptor (GIPR) to potentiate insulin release from pancreatic beta cells. GIP has also been shown to promote beta cell survival and stimulate the release of GLP-1 from islet alpha cells. There is now evidence to suggest ...
Source: Peptides - Category: Biochemistry Source Type: research
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