title: Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets.
abstract: Heat shock protein (hsp), including hsp70, 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 study, we examine the effects, in rat islets, of heat shock on insulin secretion inhibited by a small amount of NO and also on glucose metabolism, the crucial factor in insulin release. Exposure to a higher dose (15 U/ml) of interleukin-1beta (IL-1beta) abolished the insulin release by stimulation of glucose or KCl in both control and heat shocked islets. In rat islets exposed to a lower dose (1.5 U/ml) of IL-1beta, insulin secretion in response to glucose, but not to glyceraldehydes (GA), ketoisocaproate (KIC), or KCl, was selectively impaired, concomitantly with lower ATP concentrations in the presence of 16.7 mM glucose, while such suppression of insulin secretion and ATP content was not observed in heat shock-treated islets. NO production in islets exposed to 1.5 U/ml IL-1beta was significantly, but only partly, decreased by heat shock treatment. The glucose utilization rate measurement using [5-3H]-glucose and [2-3H]-glucose and the glucokinase activity in vitro were reduced in islets treated with 1.5 U/ml IL-1beta. In heat shock-treated islets, glucose utilization and glucokinase activity were not affected by 1.5 U/ml IL-1beta. 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.
authors.affiliation: Department of Metabolism and Clinical Nutrition, Kyoto University, Kyoto, Japan. takeda@metab.kuhp.kyoto-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuura
authors.forename: J
authors.initials: J
authors.lastname: Fujita
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: E
authors.initials: E
authors.lastname: Mukai
authors.forename: M
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: M
authors.initials: M
authors.lastname: Kume
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D018869:Heat-Shock Response / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D007375:Interleukin-1; D007651:Keto Acids; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005985:Glyceraldehyde; D011189:Potassium Chloride; D026423:S-Nitroso-N-Acetylpenicillamine; C013082:alpha-ketoisocaproic acid; D005941:Glucokinase; D010396:Penicillamine; D005947:Glucose