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Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance
Citation
Okamoto, H and Hribal, ML and Lin, HV and Bennett, WR and Ward, A and Accili, D, Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance, Journal of Clinical Investigation, 116, (3) pp. 775-782. ISSN 0021-9738 (2006) [Refereed Article]
DOI: doi:10.1172/JCI24967
Abstract
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 Details
Item Type: | Refereed Article |
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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 |
Downloads: | 0 |
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