Starvation refeeding experiments were conducted in rats to test the hypothesis that adaptation of glucokinase (the high Km component of glucose phosphorylation) could be the major determinant of glucose metabolism of pancreatic islet cells and of glucose-stimulated insulin release. It was found that glucokinase of islet homogenates, glucose use by intact isolated islets, and glucose-induced insulin release as studied in a perifusion system were decreased after 24 h of fasting, whereas P-fructokinase and 3-P-glyceraldehyde DH were unaltered. After extended fasting (e.g., 120 h) all three enzymes were decreased but glucose use did not change any further. Refeeding normalized all parameters. These and previous results support the concept that glucokinase serves as the adaptive beta-cell glucoreceptor relating blood glucose to insulin release.

A previous report indicating reduced glucose metabolism in pancreatic islets isolated from old as compared with young rats was reinvestigated. With a modified islet isolation procedure it was found that islets from 12- to 18-month-old rats had increased glucose use, elevated glucokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase when compared with islets from 2-month-old controls. Glucose-induced insulin release in vitro of islets from the older rats was also improved by the more careful method of islet isolation but did not achieve rates observed with islets from young rats. The data suggest an age-related activation of pancreatic islet cell metabolism, possibly in response to overstimulation by increased peripheral insulin resistance, characteristic of older obese rats.