text: Lipotoxicity impairs incretin signalling.
  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.
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entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-N
entities.text: glucose glucose glucose glucose incretin insulin glucagon-like peptide-1 incretin incretins incretin hormones incretin receptors glucose-dependent insulinotropic peptide incretin receptor insulin dipeptidyl peptidase-4 glucagon-like peptide-1 incretin