The incretin effect is defined as the higher stimulation of insulin secretion obtained when glucose is administered orally than intravenously, under similar plasma glucose levels. This effect is often totally lost in type 2 diabetic patients. The two most important incretin hormones responsible for this effect are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1. GLP-1 is a product of pre-pro-glucagon gene expression in the L-cells of the intestinal mucosa. GLP-1 potentiates glucose-induced insulin secretion, inhibits glucagon secretion but also has extrapancreatic effects and inhibits appetite and food intake. The incretins act through G protein-coupled receptors. The therapeutic potential of GLP-1 is limited by its rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4). The discovery or design of native (exenatide) or engineered GLP-1 analogues that escape DPP-4 degradation and have a prolonged half-life, as well as DPP-4 inhibitors, have markedly improved the therapeutic landscape of type 2 diabetes over the last 13 years.
This research topic will feature reviews on the structural biology, pharmacology and clinical development of GLP-1 (and related peptides) receptor agonists and multi-agonists also targeting other receptors, and of DPP-4 inhibitors.
The incretin effect is defined as the higher stimulation of insulin secretion obtained when glucose is administered orally than intravenously, under similar plasma glucose levels. This effect is often totally lost in type 2 diabetic patients. The two most important incretin hormones responsible for this effect are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1. GLP-1 is a product of pre-pro-glucagon gene expression in the L-cells of the intestinal mucosa. GLP-1 potentiates glucose-induced insulin secretion, inhibits glucagon secretion but also has extrapancreatic effects and inhibits appetite and food intake. The incretins act through G protein-coupled receptors. The therapeutic potential of GLP-1 is limited by its rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4). The discovery or design of native (exenatide) or engineered GLP-1 analogues that escape DPP-4 degradation and have a prolonged half-life, as well as DPP-4 inhibitors, have markedly improved the therapeutic landscape of type 2 diabetes over the last 13 years.
This research topic will feature reviews on the structural biology, pharmacology and clinical development of GLP-1 (and related peptides) receptor agonists and multi-agonists also targeting other receptors, and of DPP-4 inhibitors.
