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

被引：115
作者：
Piteau, Shalea
Olver, Amy
Kim, Su-Jin
Winter, Kyle
Pospisilik, John Andrew
Lynn, Francis
Manhart, Susanne
Demuth, Hans-Ulrich
Speck, Madeleine
Pederson, Raymond A.
McIntosh, Christopher H. S.
机构：
[1] Univ British Columbia, Inst Life Sci, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada
[2] Inst Mol Biotechnol, Vienna, Austria
[3] Univ Calif San Francisco, Ctr Diabet, HRI, San Francisco, CA 94143 USA
[4] Probiodrug AG, Bioctr, Halle, Germany
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 362卷 / 04期
基金：
加拿大健康研究院; 加拿大创新基金会;
关键词：
gastric inhibitory polypeptide; glucose-dependent insulinotropic polypeptide; receptor down-regulation; hyperglycemia; phlorizin; dipeptidyl peptidase IV;
D O I：
10.1016/j.bbrc.2007.08.115
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码：1007 / 1012
页数：6
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