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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Authors | Shalea Piteau, Amy Olver, Su-Jin Kim, Kyle Winter, John Andrew Pospisilik, Francis Lynn, Susanne Manhart, Hans-Ulrich Demuth, Madeleine Speck, Raymond A Pederson, Christopher H S McIntosh |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 362
Issue 4
Pg. 1007-12
(Nov 03 2007)
ISSN: 0006-291X [Print] United States |
PMID | 17803965
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Gastrointestinal Hormone
- Gastric Inhibitory Polypeptide
- gastric inhibitory polypeptide receptor
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Topics |
- Animals
- Diabetes Mellitus, Type 2
(drug therapy, metabolism)
- Dose-Response Relationship, Drug
- Down-Regulation
(drug effects)
- Drug Resistance
- Gastric Inhibitory Polypeptide
(administration & dosage)
- Hyperglycemia
(drug therapy, metabolism)
- Insulin Resistance
- Rats
- Rats, Zucker
- Receptors, Gastrointestinal Hormone
(metabolism)
- Treatment Outcome
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