Crosstalk between advanced glycation end products AGEs-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complicationsReport as inadecuate




Crosstalk between advanced glycation end products AGEs-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 14:2

First Online: 13 January 2015Received: 19 November 2014Accepted: 05 January 2015

Abstract

Advanced glycation end products AGEs consist of heterogenous group of macroprotein derivatives, which are formed by non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids, and whose process has progressed at an accelerated rate under diabetes. Non-enzymatic glycation and cross-linking of protein alter its structural integrity and function, contributing to the aging of macromolecules. Furthermore, engagement of receptor for AGEs RAGE with AGEs elicits oxidative stress generation and subsequently evokes proliferative, inflammatory, and fibrotic reactions in a variety of cells. Indeed, accumulating evidence has suggested the active involvement of accumulation of AGEs in diabetes-associated disorders such as diabetic microangiopathy, atherosclerotic cardiovascular diseases, Alzheimer’s disease and osteoporosis. Glucagon-like peptide-1 GLP-1 and glucose-dependent insulinotropic polypeptide GIP are incretins, gut hormones secreted from the intestine in response to food intake, both of which augment glucose-induced insulin release, suppress glucagon secretion, and slow gastric emptying. Since GLP-1 and GIP are rapidly degraded and inactivated by dipeptidyl peptidase-4 DPP-4, inhibition of DPP-4 and-or DPP-4-resistant GLP-1 analogues have been proposed as a potential target for the treatment of diabetes. Recently, DPP-4 has been shown to cleave multiple peptides, and blockade of DPP-4 could exert diverse biological actions in GLP-1- or GIP-independent manner. This article summarizes the crosstalk between AGEs-RAGE axis and DPP-4-incretin system in the development and progression of diabetes-associated disorders and its therapeutic intervention, especially focusing on diabetic vascular complications.

KeywordsAGEs RAGE Incretin DPP-4 Oxidative stress  Download fulltext PDF



Author: Sho-ichi Yamagishi - Kei Fukami - Takanori Matsui

Source: https://link.springer.com/article/10.1186/s12933-015-0176-5



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