EFFECT OF 48-HOUR GLUCOSE-INFUSION INTO RATS ON ISLET ION FLUXES, ATPADP RATIO AND REDOX RATIOS OF PYRIDINE-NUCLEOTIDES/

Glucose infusion into rats has been shown to sensitize/desensitize ins ulin secretion in response to glucose. In pancreatic islets from gluco se-infused rats (GIR) (48 h, 50%, 2 ml/h) basal insulin release (2.8 m mol/l glucose) was more than fourfold compared with islets from saline -infused controls and the concentration-response curve for glucose was shifted to the left with a maximum at 11.1 mmol/l. The concentration- response curve for Ca-45(2+) uptake was also shifted to the left in is lets from GIR with a maximum at 11.1 mmol/l glucose, Starting from a h igh basal level at 2.8 mmol/l glucose KCl produced no insulin release or Ca-45(2+) uptake in islets from GIR. Islets from GIR exhibited a hi gher ATP/ADP ratio in the presence of 2.8 mmol/l glucose and marked in hibition of Rb-86(+) efflux occurred even at 3 mmol/l glucose, Moreove r, in islets from GIR the redox ratios of pyridine nucleotides were in creased. On the other hand insulin content was reduced to about 20%. T he data suggest that a 48-h glucose infusion sensitizes glucose-induce d insulin release in vitro in concentrations below 11.1 mmol/l. This m ay, at least in part, be due to enhanced glucose metabolism providing increased availability of critical metabolic factors including ATP whi ch, in turn, decrease the threshold for depolarization and therefore c alcium uptake. Calcium uptake may then be further augmented by elevati on of the redox state of pyridine nucleotides.