Regulation of human beta-cell adhesion, motility, and insulin secretion by collagen IV and its receptor alpha1beta1.
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.
Department of Pediatrics, Islet Research Laboratory at The Whittier Institute for Diabetes, University of California at San Diego, La Jolla, CA 92037, USA.
Thomas
T
Kaido
Mayra
M
Yebra
Vincenzo
V
Cirulli
Anthony M
AM
Montgomery
D000368:Aged; D002448:Cell Adhesion; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D024141:Collagen Type IV / Q000502:physiology*; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010179:Pancreas / Q000196:embryology; D013997:Time Factors
D024141:Collagen Type IV; D007328:Insulin; D039222:Integrin alpha1beta1; D016023:Integrins; D003094:Collagen; D005947:Glucose