Regulation of human beta-cell adhesion, motility, and insulin secretion by collagen IV and its receptor alpha1beta1

J Biol Chem. 2004 Dec 17;279(51):53762-9. doi: 10.1074/jbc.M411202200. Epub 2004 Oct 12.


Collagens have been shown to influence the survival and function of cultured beta-cells; however, the utilization and function of individual collagen receptors in beta-cells is largely unknown. The integrin superfamily contains up to five collagen receptors, but we have determined that alpha(1)beta(1) is the primary receptor utilized by both fetal and adult beta-cells. Cultured beta-cells adhered to and migrated on collagen type IV (Col-IV), and these responses were mediated almost exclusively by alpha(1)beta(1). The migration of cultured beta-cells to Col-IV significantly exceeded that to other matrix components suggesting that this substrate is of unique importance for beta-cell motility. The interaction of alpha(1)beta(1) with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. A subset of beta-cells in developing islets was confirmed to express alpha(1)beta(1), and this expression co-localized with Col-IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate that alpha(1)beta(1) and Col-IV contribute to beta-cell functions known to be important for islet morphogenesis and glucose homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Adhesion
  • Cell Movement
  • Cell Separation
  • Cell Survival
  • Cells, Cultured
  • Collagen / metabolism
  • Collagen Type IV / physiology*
  • Flow Cytometry
  • Glucose / metabolism
  • Humans
  • Immunohistochemistry
  • Insulin / metabolism*
  • Insulin Secretion
  • Integrin alpha1beta1 / metabolism*
  • Integrins / metabolism
  • Islets of Langerhans / metabolism*
  • Microscopy, Fluorescence
  • Middle Aged
  • Pancreas / embryology
  • Time Factors


  • Collagen Type IV
  • Insulin
  • Integrin alpha1beta1
  • Integrins
  • Collagen
  • Glucose