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Diabetologia. 2013 Feb;56(2):231-3. doi: 10.1007/s00125-012-2788-6. Epub 2012 Nov 28.

Lipotoxicity impairs incretin signalling.

Author information

1
Montreal Diabetes Research Center, CRCHUM, Technopôle Angus, 2901 Rachel Est, Montréal, QC, Canada. vincent.poitout@umontreal.ca

Abstract

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.

PMID:
23188391
PMCID:
PMC3537857
DOI:
10.1007/s00125-012-2788-6
[Indexed for MEDLINE]
Free PMC Article

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