Author: ["Tohru Uchida","Takehiro Nakamura","Naoko Hashimoto","Tomokazu Matsuda","Ko Kotani","Hiroshi Sakaue","Yoshiaki Kido","Yoshitake Hayashi","Keiichi I Nakayama","Morris F White","Masato Kasuga"]
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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.Cite this article
Uchida, T., Nakamura, T., Hashimoto, N. et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat Med 11, 175–182 (2005). https://doi.org/10.1038/nm1187 