title: Update on incretin hormones.
abstract: The incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the intestine following oral ingestion of nutrients. Incretins promote insulin secretion, while GLP-1 also inhibits glucagon release and gastric emptying, minimizing postprandial glucose excursions. The incretins share similar effects on the pancreatic β cell; however, there are a number of differences in extrapancreatic actions. Type 2 diabetes (T2DM) is associated with abnormal incretin physiology, and although treatment with GIP is ineffective, GLP-1 effects are preserved. The current incretin-based approaches to T2DM include the GLP-1 agonists that are resistant to the serine protease dipeptidylpeptidase-4 (DPP4), which normally rapidly degrades the incretins, and DPP4 inhibitors (DPP4i). Incretin-based treatments have provoked much interest due to use-associated weight loss (GLP-1 agonists), minimal hypoglycemia, and potential for positive effects on pancreatic β cell biology and the cardiovascular system. However, the long-term safety of these agents has yet to be established. This review outlines the current understanding of incretin biology, available data pertaining to incretin-based treatment in T2DM, and differences between GLP-1 and DPP4i therapy.
authors.affiliation: Mater Medical Research Institute, Brisbane, Australia. University of Queensland, Brisbane, QLD, Australia.
authors.forename: Liza K
authors.initials: LK
authors.lastname: Phillips
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Prins
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000819:agonists / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D052216:Glucagon-Like Peptide 1; C041086:gastric inhibitory polypeptide receptor; D005947:Glucose