title: Lipotoxicity impairs incretin signalling.
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.
authors.affiliation: Montreal Diabetes Research Center, CRCHUM, Technopôle Angus, 2901 Rachel Est, Montréal, QC, Canada. vincent.poitout@umontreal.ca
authors.forename: V
authors.initials: V
authors.lastname: Poitout
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018027:Receptors, Glucagon / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon