Document Detail


Lipotoxicity impairs incretin signalling.
MedLine Citation:
PMID:  23188391     Owner:  NLM     Status:  MEDLINE    
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:  Comment; Journal Article     Date:  2012-11-28
Journal Detail:
Title:  Diabetologia     Volume:  56     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-06-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  231-3     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism*
Fatty Acids, Nonesterified / metabolism*
Incretins / therapeutic use*
Insulin-Secreting Cells / drug effects*,  metabolism*
Male
Receptors, Glucagon / metabolism*
Grant Support
ID/Acronym/Agency:
R01 DK058096/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Incretins; 0/Receptors, Glucagon; 0/glucagon-like peptide-1 receptor
Comments/Corrections
Comment On:
Diabetologia. 2013 Feb;56(2):423-33   [PMID:  23188390 ]

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