Document Detail


Pharmacological profile of lixisenatide: A new GLP-1 receptor agonist for the treatment of type 2 diabetes.
MedLine Citation:
PMID:  20570597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ulrich Werner; Guido Haschke; Andreas W Herling; Werner Kramer
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-06-02
Journal Detail:
Title:  Regulatory peptides     Volume:  164     ISSN:  1873-1686     ISO Abbreviation:  Regul. Pept.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-23     Completed Date:  2011-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  58-64     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. ulrich.werner@sanofi-aventis.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetes Mellitus, Type 2 / drug therapy*
Humans
Hypoglycemic Agents / therapeutic use*
Peptides / therapeutic use*
Receptors, Glucagon / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Peptides; 0/Receptors, Glucagon; 0/ZP10A peptide; 0/glucagon-like peptide receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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