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.

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

“…After secretion, levels of intact circulating GLP‐1 and GIP drop rapidly as a result of enzymatic inactivation by DPP‐4 and renal clearance. For that reason, in the circulation the half‐life of bioactive GLP‐1 is less than 2 min, that of GIP is 7 min12. In pancreatic β‐cells, GLP‐1 and GIP bind to their G‐protein coupled receptors, GLP‐1 receptor (GLP‐1R) and GIP receptor (GIPR)12.…”

“…Also, GLP‐1 reduces food intake and promotes satiety16, 17. Studies on the extrapancreatic effects of GIP are relatively scarce, but it is known that GIP is involved in lipogenesis in adipose tissue12, 14.…”

Mechanism of impaired glucose metabolism during nilotinib therapy in patients with chronic myelogenous leukemia

“…B-cell function, as calculated by HOMA2-B%, as well as the secretion of incretins (GLP-1 and GIP), which are postprandial enhancers of insulin production, 5 were not affected by nilotinib administration (P=0.922, P=0.106, and P=0.922, respectively) ( Table 2, Online Supplementary Figure S1). However, when we compared B-cell function at the start and after three months of nilotinib therapy (calculated as HOMA2-B%3 moths -HOMA2-B%start), we Figure S2).…”

Effects of a high-fat meal on postprandial incretin responses, appetite scores and ad libitum energy intake in women with obesity

“…Previous studies with high-fat meals also used this same percentage of energy from fat (20,21). Our aim with the high-fat meal was to elicit a sharp rise in the TG levels and stimulate physiological GIP and GLP-1 secretion (22,23).…”