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Cited by 36Diabetes Treatment and ManagementPancreatic function and diabetesRegulation of Appetite and Obesity

Searching for the physiological role of glucose‐dependent insulinotropic polypeptide

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Holst, Jens Juul, Windeløv, Johanne Agerlin, Boer, Geke Aline, Pedersen, Jens, Svendsen, Berit, Christensen, Mikkel, Torekov, Signe, Asmar, Meena +2 more·2016·Journal of Diabetes Investigation
DOI 10.1111/jdi.12488PMC PMC4854498
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Abstract

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.

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  • The precise effects of GIP on lipid metabolism are currently unclear; some studies suggest it may increase lipid uptake in adipose tissue and decrease lipolysis, while others suggest GIP may have lipolytic activity.

    “The precise effects of GIP on lipid metabolism are currently unclear; some studies suggest it may increase lipid uptake in adipose tissue and decrease lipolysis [53,54], while others suggest GIP may have lipolytic activity, as adipose tissue from transgenic mice overexpressing GIP has been found to be resistant to high-fat feeding [55,56].”

    From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [55]

    The “GIP and Lipid Metabolism” section says lipid uptake in adipose tissue is often assumed and that GIP may have lipolytic activity, while emphasizing uncertainty about its effects. It does not establish decreased lipolysis. It reports resistance to diet-induced obesity in mice lacking the GIP receptor, not in mice overexpressing GIP; the copy provides no page number for this section. (LLM, conf=0.88)

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Research works printed but not linked: 35

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Cited by

Sorted by citations

Authors
Holst, J. J., Windeløv, J. A., Boer, G. A., Pedersen, J., Svendsen, B., Christensen, M., Torekov, S., Asmar, M., Hartmann, B., & Nissen, A.
Affiliations
University of Copenhagen (DK)
Corresponding author
Holst, Jens Juul
ORCID
Venue
Journal of Diabetes Investigation
Publisher
Wiley
Published
2016-04
Volume
7
Issue
S1
Pages
8-12
ISSN
  • 2040-1116 (ISSN-L)
  • 2040-1124
DOI
10.1111/jdi.12488
PMC
PMC4854498
OpenAlex
W2339874459
Cited by
36
References
4
Citations by year
2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 5 · 2017: 7
FWCI
0.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes Investigation (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
Funders
Novo Nordisk Fonden (NNF16OC0019968)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
glucose-dependent insulinotropic polypeptide, GIP receptor, incretins, glucagon secretion, type 2 diabetes, impaired glucose tolerance, lipid metabolism, diet-induced obesity, bone metabolism, bone resorption, fracture risk, GIP receptor antagonist
MeSH terms
Animals, Bone and Bones, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Glucagon, Humans, Receptors, Gastrointestinal Hormone, Enteroendocrine Cells, Lipid Metabolism

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