期刊
ENDOCRINOLOGY
卷 153, 期 10, 页码 4593-4599出版社
ENDOCRINE SOC
DOI: 10.1210/en.2012-1243
关键词
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资金
- National Institutes of Health [RO1 DK67536]
- AstraZeneca
The glitazone class of insulin-sensitizing agents act, in part, by the activation of peroxisome proliferator-activated receptor (PPAR)-gamma in adipocytes. However, it is unclear whether the expression of PPAR gamma in the islets is essential for their potential beta-cell-sparing properties. To investigate the in vivo effects of rosiglitazone on beta-cell biology, we used an inducible, pancreatic and duodenal homeobox-1 enhancer element-driven, Cre recombinase to knockout PPAR gamma expression specifically in adult beta-cells (PPARgKO). Subjecting the PPARgKO mice to a chow diet led to virtually undetectable changes in glucose or insulin sensitivity, which was paralleled by minimal changes in islet gene expression. Similarly, challenging the mutant mice with a high-fat diet and treatment with rosiglitazone did not alter insulin sensitivity, glucose-stimulated insulin secretion, islet size, or proliferation in the knockout mice despite PPAR gamma-dependent and -independent changes in islet gene expression. These data suggest that PPAR gamma expression in the beta-cells is unlikely to be directly essential for normal beta-cell function or the insulin-sensitizing actions of rosiglitazone. (Endocrinology 153: 4593-4599, 2012)
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