Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
- 30 January 2005
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 11 (2) , 175-182
- https://doi.org/10.1038/nm1187
Abstract
The protein p27Kip1 regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). Here we show that p27Kip1 progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2−/−) or the long form of the leptin receptor (Lepr−/− or db/db). Deletion of the gene encoding p27Kip1 (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation. Thus, p27Kip1 contributes to beta-cell failure during the development of type 2 diabetes in Irs2−/− and Lepr−/− mice and represents a potential new target for the treatment of this condition.Keywords
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