Starvation diabetes in the rat: onset, recovery, and specificity of reduced responsiveness of pancreatic beta-cells.

A 24-h starvation markedly diminished the stimulant action of 8 mM glucose on insulin secretion from isolated perifused rat islets of Langerhans. The response to a supramaximal glucose stimulus (27.5 mM) remained normal, but prolonged fasting (48 or more) also reduced its efficacy. Refeeding of 24-h fasted animals resulted in complete restoration of glucose sensitivity within 24 h. The responses to glyceraldehyde (2 mM) and alpha-ketoisocaproate (8 mM) at concentrations which elicit approximately half-maximal stimulation were unaltered by a 24-h fast, while that to a half-maximally effective dose of mannose (15 mM) was decreased. Theophylline (5 mM) could not normalize the reduced secretory response to glucose seen in this state. The islets' ability to metabolize glucose, using various in vitro pretreatment protocols and different incubation times, was not affected by a 24-h fast. Mannose and glyceraldehyde metabolism were also unaltered. Prolonged fasting (48 h) reduced glucose metabolism by 25% at both 8 and 27.5 mM. The acute adaptive changes in islet sensitivity to moderate glucose and mannose concentrations during short term fasting (24 h) cannot be explained by an altered usage of the added hexoses.