Document Detail


The significance of GPR119 agonists as a future treatment for type 2 diabetes.
MedLine Citation:
PMID:  20862393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GPR119 is a G protein-coupled receptor that is expressed on only a limited number of tissues, including pancreatic β-cells and enteroendocrine cells in the small intestine, and that appears to be involved in the regulation of metabolic homeostasis. The protein was originally defined as an orphan receptor, but it has subsequently been shown to bind a variety of lipid-derived ligands, as well as a range of small synthetic molecules. There is still debate as to the identity of its principal endogenous ligand, but certain lysophospholipids species, various fatty acyl-ethanolamides and N-oleoyldopamine have all been proposed as potential agonists. GPR119 is coupled to the signal transducer Gαs and activation of the receptor leads to increased adenylate cyclase activity via Gαs and a rise in intracellular cAMP. This then potentiates glucose-induced insulin secretion or promotes the release of intestinal incretin hormones, according to cell type. Both mechanisms ultimately lead to a rise in insulin secretion (either directly or indirectly) and improved glucose control. Thus, GPR119 may represent an important new therapeutic target for the design of insulin secretagogues able to promote improvements in blood glucose control in patients with type 2 diabetes. Accordingly, a range of lead compounds are in development as potential therapeutic agents.
Authors:
Shalinee Dhayal; Noel G Morgan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Drug news & perspectives     Volume:  23     ISSN:  0214-0934     ISO Abbreviation:  Drug News Perspect.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-23     Completed Date:  2011-01-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809164     Medline TA:  Drug News Perspect     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-24     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.
Affiliation:
Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Plymouth, Plymouth, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / drug effects
Diabetes Mellitus, Type 2 / drug therapy*,  physiopathology
Drug Delivery Systems
Drug Design
Humans
Hypoglycemic Agents / pharmacology*
Insulin / secretion
Ligands
Receptors, G-Protein-Coupled / agonists*
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/GPR119 protein, human; 0/Hypoglycemic Agents; 0/Ligands; 0/Receptors, G-Protein-Coupled; 11061-68-0/Insulin

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


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