LOSS OF GLUCOSE-INDUCED INSULIN-SECRETION AND GLUT2 EXPRESSION IN TRANSPLANTED BETA-CELLS

Either 200 or 400 syngeneic islets were transplanted under the kidney capsule of normal or streptozocin-induced diabetic B6/AF1 mice, The di abetic mice with 400 islets became normoglycemic, but those with 200 i slets, an insufficient number, were still diabetic after the transplan tation (Tx), Two weeks after Tx, GLUT2 expression in the islet grafts was evaluated by immunofluorescence and Western blots, and graft funct ion was examined by perfusion of the graft-bearing kidney. Immunofluor escence for GLUT2 was dramatically reduced in the beta-cells of grafts with 200 islets exposed to hyperglycemia. However, it was plentiful i n grafts with 400 islets in a normoglycemic environment, Densitometric analysis of Western blots on graft homogenates demonstrated that GLUT 2 protein levels in the islets, when exposed to chronic hyperglycemia for 2 weeks, were decreased to 16% of those of normal recipients, More over, these grafts had defective glucose-induced insulin secretion, wh ile the effects of arginine were preserved, We conclude that GLUT2 exp ression in normal beta-cells is promptly downregulated during exposure to hyperglycemia and may contribute to the loss of glucose-induced in sulin secretion of diabetes.