Open AccessSearching for the physiological role of glucose‐dependent insulinotropic polypeptide
Author(s) -
Holst Jens Juul,
Windeløv Johanne Agerlin,
Boer Geke Aline,
Pedersen Jens,
Svendsen Berit,
Christensen Mikkel,
Torekov Signe,
Asmar Meena,
Hartmann Bolette,
Nissen Anne
Publication year - 2016
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12488
Subject(s) - incretin , endocrinology , medicine , gastric inhibitory polypeptide , receptor , carbohydrate metabolism , hormone , type 2 diabetes , insulin resistance , glucagon like peptide 1 , glucagon receptor , diabetes mellitus , glucagon
Glucose‐dependent insulinotropic polypeptide ( GIP ) was established as a gut hormone more than 40 years ago, and there is good experimental support for its role as an incretin hormone although deletion of the GIP receptor or the GIP cells or GIP receptor mutations have only minor effects on glucose metabolism. Unlike the related hormone, GLP ‐1, GIP stimulates the secretion of glucagon, which in healthy individuals may help to stabilize glucose levels, but in people with type 2 diabetes may contribute to glucose intolerance. A role in lipid metabolism is supported by numerous indirect observations and by resistance to diet‐induced obesity after deletion of the GIP receptor. However, a clear effect on lipid clearance could not be identified in humans, raising doubt about its importance. The GIP receptor is widely expressed in the body and also appears to be expressed on bone cells, and experimental studies in rodent point to effects on bone metabolism. Recent studies revealed pronounced inhibitory effects of GIP on bone resorption markers in humans and suggest that GIP may be (one of the) gastrointestinal regulators of bone turn‐over. In support of this, a loss‐of‐function GIP receptor mutation in humans is associated with a marked increase in fracture risk. The lack of a reliable GIP receptor antagonist contributes to the uncertainty regarding the physiological role of GIP .