Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice

被引：178

作者：

Uchida, T

Nakamura, T

Hashimoto, N

Matsuda, T

Kotani, K

Sakaue, H

Kido, Y

Hayashi, Y

Nakayama, KI

White, MF

Kasuga, M

机构：

[1] Kobe Univ, Grad Sch Med, Div Diabet & Digest & Kidney Dis, Dept Clin Mol Med,Chuo Ku, Kobe, Hyogo 6500017, Japan

[2] Kobe Univ, Grad Sch Med, Div Mol Med & Med Genet, Int Ctr Med Res, Kobe, Hyogo 6500017, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan

[4] Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA

来源：

NATURE MEDICINE | 2005年 / 11卷 / 02期

关键词：

D O I：

10.1038/nm1187

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：

The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). Here we show that p27(Kip1) 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 p27(Kip1) (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, p27(Kip1) 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.

引用

页码：175 / 182

页数：8

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