THE ROLE OF OLD-AGE IN THE EFFECTS OF GLUCOSE ON INSULIN-SECRETION, PENTOSEPHOSPHATE SHUNT ACTIVITY, PYRIDINE-NUCLEOTIDES AND GLUTATHIONE OF RAT PANCREATIC-ISLETS

In pancreatic islets of adult (3 mo.) and old (24 mo.) rats, the effect of glucose on glucose oxidation, pyridine nucleotides, glutathione [GSSG] and insulin secretion was studied. DNA content was similar in both groups of animals; however, islets of old rats exhibited 30% less insulin content. While glucose-induced (16.7 mM) insulin secretion in islets of old rats was .apprx. 50% less than in islets of adults, no significant difference was observed in the insulin-releasing effect of theophylline (1 mM). Although islet production of 14CO2 in the presence of 16.7 mM glucose increased equally in both groups, elevation of glucose failed to increase the percentage of total glucose oxidation via the pentose phosphate shunt in islets of old rats. Elevation of glucose increased the NADPH/NADP and the NADH/NAD ratio in both groups of islets in a similar manner. The effect of glucose on the GSH[reduced glutathione]/GSSG ratio revealed a dose-related increase in the islets of adult rats; islets of old rats did not respond to elevation of glucose. The lower secretory response of islets of old rats is related to the failure of glucose to increase the GSH/GSSG ratio. In contrast, the insulin release induced by theophylline does not appear to depend on islet thiols.