Author: Werner, U.; Haschke, G.; Herling, A.W.; Kramer, W.
Description: The glucagon-like peptide-1 (GLP-1) receptor represents an established therapeutic target in type 2 diabetes mellitus (T2DM). Agents that activate this receptor improve glucose tolerance alongside a low risk of hypoglycaemia, and have the potential to modify disease progression. Lixisenatide is a new potent and selective GLP-1 receptor agonist currently in development. The preclinical pharmacological profile of Lixisenatide suggests actions that are highly relevant to the long-term maintenance of glucose homeostasis. Lixisenatide protected Ins-1 cells (a rat-derived beta-cell line) from both lipid- and cytokine-induced apoptosis. More importantly, Lixisenatide also prevented lipotoxicity-induced insulin depletion in human islets and preserved insulin production, storage and pancreatic beta-cell function in vitro. Enhancement of insulin biosynthesis and pancreatic beta-cell volume could also be demonstrated in animal models of type 2 diabetes. The improvement of glucose-stimulated insulin secretion provided by Lixisenatide occurred in a strictly glucose-dependent manner. In animal models of diabetes, Lixisenatide improved basal blood glucose and HbA(1c) with a rapid onset and sustained duration of action, and prevented the deterioration of pancreatic responsiveness and glucose homeostasis. Lixisenatide also delayed gastric emptying and reduced food intake. The efficacy/safety profile of Lixisenatide is currently being studied further in an extensive ongoing Phase III clinical study programme. This article reviews the preclinical pharmacological profile of Lixisenatide.
Subject Headings: Animals; Diabetes Mellitus, Type 2/drug therapy; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents/therapeutic use; Peptides/therapeutic use; Receptors, Glucagon/antagonists & inhibitors
Publication year: 2010
Journal or book title: Regulatory Peptides
Volume: 164
Issue: 2-3
Pages: 58-64
Find the full text : https://www.sciencedirect.com/science/article/pii/S0167011510001163
Find more like this one (cited by): https://scholar.google.com/scholar?cites=15387978019662214591&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 2635