Document Detail


Lipotoxicity impairs incretin signalling.
MedLine Citation:
PMID:  23188391     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide are secreted by enteroendocrine cells and augment glucose-induced insulin secretion in response to food ingestion in a glucose-dependent manner. This mechanism forms the basis for incretin-based therapies in type 2 diabetes. However, the insulinotropic effect of incretins is diminished in type 2 diabetic patients, due in part to reduced expression of incretin receptors as a consequence of glucotoxicity. In this issue of Diabetologia, Kang et al (DOI: 10.1007/s00125-012-2776-x ) provide evidence that in addition to glucotoxicity, lipotoxicity also affects incretin receptor expression and signalling in insulin-secreting cells and isolated islets. In animal models of diabetes, the authors show that co-administration of a lipid-lowering drug with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 agonist improved glucose tolerance and beta cell mass. These novel findings provide convincing support for the notion that restoring normal circulating lipid levels in type 2 diabetes might help improve the efficacy of incretin-based therapies.
Authors:
V Poitout
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-28
Journal Detail:
Title:  Diabetologia     Volume:  -     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Montreal Diabetes Research Center, CRCHUM, Technopôle Angus, 2901 Rachel Est, Montréal, QC, Canada, H1W 4A4, vincent.poitout@umontreal.ca.
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