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Conditional β1‐integrin‐deficient mice display impaired pancreatic β cell function
Author(s) -
Riopel M.,
Krishnamurthy M.,
Li J.,
Liu S.,
Leask A.,
Wang R.
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2849
Subject(s) - conditional gene knockout , integrin , endocrinology , medicine , biology , collagen receptor , cell growth , protein kinase b , phosphorylation , microbiology and biotechnology , cell , phenotype , biochemistry , genetics , gene
Abstract β1‐Integrin, a critical regulator of β cell survival and function, has been shown to protect against cell death and promote insulin expression and secretion in rat and human islet cells in vitro . The aim of the present study was to examine whether the knockout of β1‐integrin in collagen I‐producing cells would have physiological and functional implications in pancreatic endocrine cells in vivo . Using adult mice with a conditional knockout of β1‐integrin in collagen I‐producing cells, the effects of β1‐integrin deficiency on glucose metabolism and pancreatic endocrine cells were examined. Male β1‐integrin‐deficient mice display impaired glucose tolerance, with a significant reduction in pancreatic insulin content ( p < 0.01). Morphometric analysis revealed a significant reduction in β cell mass ( p < 0.001) in β1‐integrin‐deficient mice, along with a significant decrease in β cell proliferation, Pdx‐1 and Nkx6.1 expression when compared with controls. Interestingly, these physiological and morphometric alterations in female β1‐integrin‐deficient mice were less significant. Furthermore, β1‐integrin‐deficient mice displayed decreased FAK ( p < 0.05) and ERK1/2 ( p < 0.001) phosphorylation, reduced cyclin D1 levels ( p < 0.001) and increased caspase 3 cleavage ( p < 0.01), while no changes in Akt phosphorylation were observed, indicating that the β1‐integrin signals through the FAK–MAPK–ERK pathway in vivo . Our results demonstrate that β1‐integrin is involved in the regulation of glucose metabolism and contributes to the maintenance of β cell survival and function in vivo . Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.