Diabetes is associated with defective β cell function and altered β cell mass. The mechanisms regulating β cell mass and its adaptation to insulin resistance are unknown. It is unclear whether compensatory β cell hyperplasia is achieved via proliferation of existing β cells or neogenesis from progenitor cells embedded in duct epithelia. We have used transgenic mice expressing a mutant form of the forkhead-O1 transcription factor (FoxO1) in both pancreatic ductal and endocrine β cells to assess the contribution of these 2 compartments to islet expansion. We show that the mutant FoxO1 transgene prevents β cell replication in 2 models of β cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion. In contrast, we failed to detect a specific effect of the FoxO1 transgene on the number of periductal β cells. We propose that β cell compensation to insulin resistance is a proliferative response of existing β cells to growth factor signaling and requires FoxO1 nuclear exclusion.

Item Type:	Refereed Article
Research Division:	Biological Sciences
Research Group:	Genetics
Research Field:	Developmental genetics (incl. sex determination)
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Bennett, WR (Dr Bill Bennett)
ID Code:	63718
Year Published:	2006
Web of Science® Times Cited:	90
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2010-05-26
Last Modified:	2010-05-26
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