INS-1 cell glucose-stimulated insulin secretion is reduced by the downregulation of the 67 kDa laminin receptor.
Understanding β cell-extracellular matrix (ECM) interactions can advance our knowledge of the mechanisms that control glucose homeostasis and improve culture methods used in islet transplantation for the treatment of diabetes. Laminin is the main constituent of the basement membrane and is involved in pancreatic β cell survival and function, even enhancing glucose-stimulated insulin secretion. Most of the studies on cell responses towards laminin have focused on integrin-mediated interactions, while much less attention has been paid on non-integrin receptors, such as the 67 kDa laminin receptor (67LR). The specificity of the receptor-ligand interaction through the adhesion of INS-1 cells (a rat insulinoma cell line) to CDPGYIGSR-, GRGDSPC- or CDPGYIGSR + GRGDSPC-covered surfaces was evaluated. Also, the effects of the 67LR knocking down over glucose-stimulated insulin secretion were investigated. Culture of the INS-1 cells on the bioactive surfaces was improved compared to the low-fouling carboxymethyl dextran (CMD) surfaces, while downregulation of the 67LR resulted in reduced cell adhesion to surfaces bearing the CDPGYIGSR peptide. Glucose-stimulated insulin secretion was hindered by downregulation of the 67LR, regardless of the biological motif available on the biomimetic surfaces on which the cells were cultured. This finding illustrates the importance of the 67LR in glucose-stimulated insulin secretion and points to a possible role of the 67LR in the mechanisms of insulin secretion.
Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.|Research Centre on Aging, Institut universitaire de gériatrie de Sherbrooke, Sherbrooke, QC, Canada.
Georges
G
Sabra
Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.|Research Centre on Aging, Institut universitaire de gériatrie de Sherbrooke, Sherbrooke, QC, Canada.
Evan A
EA
Dubiel
Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.|Research Centre on Aging, Institut universitaire de gériatrie de Sherbrooke, Sherbrooke, QC, Canada.
Carina
C
Kuehn
CIHR Team on Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Taoufik
T
Khalfaoui
CIHR Team on Digestive Epithelium, Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Jean-François
JF
Beaulieu
Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, QC, Canada.|Research Centre on Aging, Institut universitaire de gériatrie de Sherbrooke, Sherbrooke, QC, Canada.
Patrick
P
Vermette
D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017474:Receptors, Laminin / Q000819:agonists* / Q000096:biosynthesis
D007328:Insulin; D010455:Peptides; D017474:Receptors, Laminin; D005947:Glucose
67 kDa laminin receptor; INS-1 cells; YIGSR; diabetes; insulin secretion; laminin