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.
Kaido
Thomas
T
Department of Pediatrics, Islet Research Laboratory at The Whittier Institute for Diabetes, University of California at San Diego, La Jolla, CA 92037, USA.
Yebra
Mayra
M
Cirulli
Vincenzo
V
Montgomery
Anthony M
AM
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