Inhibition of GSK3 promotes replication and survival of pancreatic beta cells

被引：121

作者：

Mussmann, Rainer ^{[1
]}

Geese, Marcus ^{[1
]}

Harder, Friedrich ^{[1
]}

Kegel, Simone ^{[1
]}

Andag, Uwe ^{[1
]}

Lomow, Alexander ^{[1
]}

Burk, Ulrike ^{[1
]}

Onichtchouk, Daria ^{[1
]}

Dohrmann, Cord ^{[1
]}

Austen, Matthias ^{[1
]}

机构：

[1] DeveloGen AG, D-37079 Gottingen, Germany

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2007年 / 282卷 / 16期

关键词：

D O I：

10.1074/jbc.M609637200

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：

Recent developments indicate that the regeneration of beta cell function and mass in patients with diabetes is possible. A regenerative approach may represent an alternative treatment option relative to current diabetes therapies that fail to provide optimal glycemic control. Here we report that the inactivation of GSK3 by small molecule inhibitors or RNA interference stimulates replication of INS-1E rat insulinoma cells. Specific and potent GSK3 inhibitors also alleviate the toxic effects of high concentrations of glucose and the saturated fatty acid palmitate on INS-1E cells. Furthermore, treatment of isolated rat islets with structurally diverse small molecule GSK3 inhibitors increases the rate beta cell replication by 2-3-fold relative to controls. We propose that GSK3 is a regulator of beta cell replication and survival. Moreover, our results suggest that specific inhibitors of GSK3 may have practical applications in beta cell regenerative therapies.

引用

收藏

页码：12030 / 12037

页数：8

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