Defective Glucose-Dependent Insulinotropic Polypeptide Receptor Expression in Diabetic Fatty Zucker Rats
Open accessAbstract
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic β-cell. In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. Yet, there has been no conclusive evidence suggesting that GIP levels are elevated in diabetes. The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. This hypothesis was tested using a strain of diabetic fatty Zucker rats. The obese rats displayed basal GIP levels similar to the control animals; however, they were unresponsive to a GIP infusion (4 pmol · min–1 · kg–1), whereas the lean animals displayed a significant reduction in blood glucose (GIP levels, 50% control after 60 min, P < 0.05) as well as a significant increase in circulating insulin. GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 ± 3.0 × basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 × control area under the curve [AUC]) from lean animals. GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. Islets from lean animals subjected to static incubations with GIP showed a 2.2-fold increase in cAMP, whereas GIP failed to increase islet cAMP in the VDF islets. Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. These data suggest that the decreased effectiveness of GIP in the VDF rat and in type 2 diabetes may be a result of a decreased receptor expression in the islet.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Beta-cell rest can at least temporarily allow insulin secretory capacity recovery.
“This study provides in vivo evidence that “beta-cell rest” can at least temporarily allow insulin secretory capacity recovery, and in vitro studies examining the effect of diazoxide on diabetic human islets produced similar findings.177”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [177]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 44 · Cited by 208
- Authors
- Lynn, F. C., Pamir, N., Ng, E. H. C., McIntosh, C. H. S., Kieffer, T. J., & Pederson, R. A.
- Affiliations
- University of British Columbia (CA)
- University of Alberta (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-05-01
- Volume
- 50
- Issue
- 5
- Pages
- 1004-1011
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2157068658
- Cited by
- 208
- References
- 44
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 3 · 2016: 9 · 2015: 11 · 2014: 7 · 2013: 7 · 2012: 8
- FWCI
- 12.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Killam Trusts
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucose-dependent insulinotropic polypeptide, GIP receptor, type 2 diabetes, pancreatic islets, insulin secretion, glucagon-like peptide-1, receptor desensitization, receptor expression, cyclic AMP, islet function
- MeSH terms
- Insulin Secretion, Animals, Blood Glucose, Carrier Proteins, Cells, Cultured, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Glucose Tolerance Test, Insulin, Islets of Langerhans, Kinetics, Perfusion, Rats, Zucker, Receptors, Cell Surface, Receptors, Gastrointestinal Hormone, Reference Values, RNA, Messenger, Transcription, Genetic, Rats, Receptors, Leptin, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
