Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes

Anita M. Hennige, Deborah J. Burks, Umut Ozcan, Rohit N. Kulkarni, Jing Ye, Sunmin Park, Markus Schubert, Tracey L. Fisher, Matt A. Dow, Rebecca Leshan, Mark Zakaria, Mahmud Mossa-Basha, Morris F. White

Research output: Contribution to journalArticlepeer-review

216 Scopus citations


The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic β cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes. Here we show that β cell-specific expression of Irs2 at a low or a high level delivered a graded physiologic response that promoted β cell growth, survival, and insulin secretion that prevented diabetes in Irs2 -/- mice, obese mice, and streptozotocin-treated mice; and that upon transplantation, the transgenic islets cured diabetes more effectively than WT islets. Thus, pharmacological approaches that promote Irs2 expression in β cells, especially specific cAMP agonists, could be rational treatments for β cell failure and diabetes.

Original languageEnglish (US)
Pages (from-to)1521-1532
Number of pages12
JournalJournal of Clinical Investigation
Issue number10
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes'. Together they form a unique fingerprint.

Cite this