An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

Abstract

Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreatic β-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

Glycation in Parkinson's disease and Alzheimer's disease

“…Other antidiabetes treatments showing promising results as therapeutic agents for PD and AD are based on the protective action of insulin‐like metabolic hormones, such as glucagon‐like peptide–1 (GLP‐1). This incretin decreases blood glucose levels and reduces the expression of RAGE . Although dipeptidyl peptidase‐4 (DPP‐4) rapidly degrades endogenous GLP‐1, its inhibition increases the levels of GLP‐1 and, consequently, activates GLP‐1 receptors that are known to elicit protective effects.…”

“…This incretin decreases blood glucose levels and reduces the expression of RAGE. 128 Although dipeptidyl peptidase-4 (DPP-4) rapidly degrades endogenous GLP-1, its inhibition increases the levels of GLP-1 and, consequently, activates GLP-1 receptors that are known to elicit protective effects. Currently, the activation of these receptors using more stable analogues of GLP-1 is being studied.…”

Il-1β, Rage and Fabp4: Targeting the Dynamic Trio in Metabolic Inflammation and Related Pathologies

“…Another group of agents capable of inhibiting RAGE signaling are Sitagliptin, Alogliptin, and Vildagliptin, the inhibitors of DPP-4 [179]. DPP-4 inhibitors are used to stabilize endogenous levels of GLP-1, an incretin hormone that regulates glucose homeostasis [179].…”

“…DPP-4 inhibitors are used to stabilize endogenous levels of GLP-1, an incretin hormone that regulates glucose homeostasis [179]. GLP-1 is rapidly inactivated by DPP-4 in circulation and restoring GLP-1 levels with DPP-4 inhibitors preserves the pancreatic β-cell function, and limits vascular complications from diabetes [179].…”

“…DPP-4 inhibitors are used to stabilize endogenous levels of GLP-1, an incretin hormone that regulates glucose homeostasis [179]. GLP-1 is rapidly inactivated by DPP-4 in circulation and restoring GLP-1 levels with DPP-4 inhibitors preserves the pancreatic β-cell function, and limits vascular complications from diabetes [179]. These agents have also been proposed to have cancer protective effects in diabetic patients via RAGE–AGE inhibition, a hypothesis currently being investigated in an observational, prospective clinical trial [207].…”