Cited by 130Pancreatic function and diabetesDiabetes Treatment and ManagementReceptor Mechanisms and Signaling

Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

Piteau, Shalea, Olver, Amy, Kim, Su-Jin, Winter, Kyle, Pospisilik, John Andrew, Lynn, Francis, Manhart, Susanne, Demuth, Hans-Ulrich +3 more·2007·Biochemical and Biophysical Research Communications

Abstract

In type 2 diabetes (T2DM) beta-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3+/-3.8%) than ZF rats (48.8+/-22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0+/-17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.

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Crossref · 10.1016/j.bbrc.2007.08.115

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Authors
Piteau, S., Olver, A., Kim, S.-J., Winter, K., Pospisilik, J. A., Lynn, F., Manhart, S., Demuth, H.-U., Speck, M., Pederson, R. A., & McIntosh, C. H. S.
Affiliations
  • University of British Columbia (CA)
  • Institute of Molecular Biotechnology (AT)
  • University of California, San Francisco (US)
  • Probiodrug (Germany) (DE)
Corresponding author
McIntosh, Christopher H.S.
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2007-11
Volume
362
Issue
4
Pages
1007-1012
ISSN
0006-291X (ISSN-L)
OpenAlex
W1964575982
Cited by
130
References
32
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 4 · 2013: 12 · 2012: 2
FWCI
8.63
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Diabetes Association
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
glucose-dependent insulinotropic polypeptide, GIP receptor, receptor down-regulation, type 2 diabetes, hyperglycemia, pancreatic islets, phloridzin, DPP-4 inhibitors, glucose tolerance, Zucker rats, glycemic control
MeSH terms
Animals, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Drug Resistance, Gastric Inhibitory Polypeptide, Hyperglycemia, Insulin Resistance, Rats, Zucker, Receptors, Gastrointestinal Hormone, Down-Regulation, Treatment Outcome, Rats

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