Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets

Heat shock protein (hsp), including hsp76, has been reported to restore the glucose-induced insulin release suppressed by nitric oxide (NO). However, the mechanism underlying this recovery remains unclear. In the present stud y, we examine the effects, in rat islets, of heat shock on insulin secretio n inhibited by a small amount of NO and also on glucose metabolism, the cru cial factor in insulin release. Exposure to a higher dose (15 U/ml) of inte rleukin-1 beta (IL-1 beta) abolished the insulin release by stimulation of glucose or KCI in both control and heat shocked islets. In rat islets expos ed to a lower dose (1.5 U/ml) of IL-1 beta, insulin secretion in response t o glucose, but not to glyceraldehydes (GA), ketoisocaproate (KIC), or KCl, was selectively impaired, concomitantly with lower ATP concentrations in th e presence of 16.7 mM glucose, while such suppression of insulin secretion and ATP content was not observed in heat shock-treated islets. NO productio n in islets exposed to 1.5 U/ml IL-1 beta was significantly, but only partl y, decreased by heat shock treatment. The glucose utilization rate measurem ent using [5-H-3]-glucose and [2-H-3]-glucose and the glucokinase activity in vitro were reduced in islets treated with 1.5 U/ml IL-1 beta. In heat sh ock-treated islets, glucose utilization and glucokinase activity were not a ffected by 1.5 U/ml IL-1 beta. These data suggest that heat shock restores glucose-induced insulin release inhibited by NO by maintaining glucokinase activity and the glucose utilization rate in islets in addition to reducing endogenous NO production. (C) 2001 Academic Press.