PANCREATIC BETA-CELL FUNCTION AND ISLET-CELL PROLIFERATION - EFFECT OF HYPERINSULINEMIA

Pancreatic beta-cell function was studied in adult female rats, in whi ch endogenous insulin demand was fully met by SC infusion of human ins ulin (4.8 IU/24 h) for 6 days, resulting in hyperinsulinaemia and seve re hypoglycaemia. The amount of pancreatic endocrine tissue declined b y 40%, (pro)insulin mRNA, as determined by in situ hybridisation by 95 %, and the amount of stored insulin by 90%. Islet-cell proliferation a s determined by 24 h of BrdU infusion declined by 60%. Basal glucose l evels normalized within 2 days after the insulin treatment was ended, whereas about 1 week was needed to restore the amount of pancreatic in sulin, glucose-induced insulin release, and glucose tolerance to norma l values. The amount of endocrine tissue recovered within 48 h and mRN A abundance within 96 h after discontinuation of the insulin infusion, whereas at that time islet-cell proliferation still showed a sixfold increase, before returning to control levels after 1 week. These resul ts show that after a period of suppression of beta-cell function, reco very of insulin synthetic capacity does not immediately result in norm alization of insulin stores and insulin release. Under these condition s, episodes of hyperglycaemia may occur, which may act as a stimulus f or islet-cell proliferation.