Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat
- University of British Columbia, Department of Cellular and Physiological Sciences, Life Sciences Institute, 2350 Health Sciences Mall, Vancouver, BC (Canada)
- Institute of Molecular Biotechnology, Vienna (Austria)
- HRI, Diabetes Center, University of California San Francisco, CA (United States)
- Probiodrug AG, Biocenter, Halle (Saale) (Germany)
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.
- OSTI ID:
- 21032954
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 362, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2007.08.115; PII: S0006-291X(07)01822-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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