Starvation refeeding experiments were conducted in rats to test the hypothesis that adaptation of glucokinase (the high K_m component of glucose phosphorylation) could be the major determinant of glucose metabolism of pancreatic islet cells and of glucosestimulated 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 β-cell glucoreceptor relating blood glucose to insulin release.