The incretin system in healthy humans: The role of GIP and GLP-1

• Published in: Metabolism, clinical and experimental clinical and experimental, 2019-07, Vol.96, p.46-55
• Main Author: Holst, Jens Juul
• Format: Article
• Language: English
• Subjects: Cytokines - physiology; Glucagon-Like Peptide 1 - physiology; Health Status; Humans; Incretins - physiology; Insulin - metabolism; Signal Transduction - physiology
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2019.04.014

The incretin effect, the amplification of insulin secretion occurring when glucose is taken in orally as compared to infused intravenously, is one of the factors that help the body to tolerate carbohydrate/glucose ingestion. These include 1) amount and type of carbohydrates; 2) gastric emptying rate; 3) digestion and absorption of the carbohydrates; 4) secretion and effect of the incretin hormones; 5) disposition of absorbed nutrients/glucose. The incretin effect can also be viewed as the fraction of the ingested glucose load handled via gastrointestinal mechanisms (including the incretin effect); it is calculated by comparison of the amount of glucose required to copy, by intravenous infusion, the oral load. Typically, for 75 g of oral glucose, about 25 g are required. This means that the GastroIntestinal Glucose Disposal (GIGD) is 66%. Both the GIGD and the incretin effect depend on the amount of glucose ingested: for higher doses the GIGD may amount to 80%, which shows that this effect is a major contributor to glucose tolerance. The main mechanism behind it is stimulation of insulin secretion by a proportional secretion of the insulinotropic hormones GIP and GLP-1. Recently it has become possible to estimate their contributions in healthy humans using specific and potent receptor antagonists. Both hormones act to improve glucose tolerance (i.e. the antagonists impair tolerance) and their effects are additive. GIP seems to be quantitatively the most important, particularly regarding insulin secretion, whereas the action of GLP-1 is mainly displayed via inhibition of glucagon secretion. •The incretin effect refers to the amplification of insulin secretion after oral versus intravenous glucose•It is responsible for the disposal of most of ingested glucose and therefore essential for glucose tolerance•The incretin effect is mainly due to the actions of the gut hormones GIP and GLP-1•Antagonist studies revealed that GIP is most important for insulin secretion, GLP-1 for inhibition of glucagon secretion