Tr. Koiter et al., PANCREATIC BETA-CELL FUNCTION AND ISLET-CELL PROLIFERATION - EFFECT OF HYPERINSULINEMIA, Physiology & behavior, 57(4), 1995, pp. 717-721
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.