Searching for the physiological role of glucose-dependent insulinotropic polypeptide
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Searching for the physiological role of glucose-dependent insulinotropic polypeptide. / Holst, Jens Juul; Windeløv, Johanne Agerlin; Boer, Geke Aline; Pedersen, Jens; Svendsen, Berit; Christensen, Mikkel; Torekov, Signe; Asmar, Meena; Hartmann, Bolette; Nissen, Anne.
In: Journal of Diabetes Investigation, Vol. 7, No. S1, 01.04.2016, p. 8-12.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Searching for the physiological role of glucose-dependent insulinotropic polypeptide
AU - Holst, Jens Juul
AU - Windeløv, Johanne Agerlin
AU - Boer, Geke Aline
AU - Pedersen, Jens
AU - Svendsen, Berit
AU - Christensen, Mikkel
AU - Torekov, Signe
AU - Asmar, Meena
AU - Hartmann, Bolette
AU - Nissen, Anne
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Bone remodeling
KW - Glucagon
KW - Lipid metabolism
UR - http://www.scopus.com/inward/record.url?scp=84963538091&partnerID=8YFLogxK
U2 - 10.1111/jdi.12488
DO - 10.1111/jdi.12488
M3 - Journal article
C2 - 27186349
AN - SCOPUS:84963538091
VL - 7
SP - 8
EP - 12
JO - Journal of Diabetes Investigation
JF - Journal of Diabetes Investigation
SN - 2040-1116
IS - S1
ER -
ID: 172853357