Conditional β1-integrin-deficient mice display impaired pancreatic β cell function

J Pathol. 2011 May;224(1):45-55. doi: 10.1002/path.2849. Epub 2011 Mar 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillaries / pathology
  • Cell Proliferation
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Gene Expression Regulation
  • Glucose Tolerance Test / methods
  • Homeodomain Proteins / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Integrin beta1 / biosynthesis
  • Integrin beta1 / genetics
  • Integrin beta1 / physiology*
  • Islets of Langerhans / blood supply
  • MAP Kinase Signaling System / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Organ Size
  • Pancreas / metabolism
  • Pancreas / pathology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Trans-Activators / metabolism
  • Weight Loss / physiology


  • Homeodomain Proteins
  • Insulin
  • Integrin beta1
  • Nkx6-1 protein, mouse
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases