title: Insulin renders diabetic rats resistant to acute ischemic stroke by arresting nitric oxide reaction with superoxide to form peroxynitrite.
abstract: BACKGROUND
  The functions of free radicals on the effects of insulin that result in protection against cerebral ischemic insult in diabetes remain undefined. This present study aims to explain the contradiction among nitric oxide (NO)/superoxide/peroxynitrite of insulin in amelioration of focal cerebral ischemia-reperfusion (FC I/R) injury in streptozotocin (STZ)-diabetic rats and to delineate the underlying mechanisms. Long-Evans male rats were divided into three groups (age-matched controls, diabetic, and diabetic treated with insulin) with or without being subjected to FC I/R injury.
  
  
  RESULTS
  Hyperglycemia exacerbated microvascular functions, increased cerebral NO production, and aggravated FC I/R-induced cerebral infarction and neurological deficits. Parallel with hypoglycemic effects, insulin improved microvascular functions and attenuated FC I/R injury in STZ-diabetic rats. Diabetes decreased the efficacy of NO and superoxide production, but NO and superoxide easily formed peroxynitrite in diabetic rats after FC I/R injury. Insulin treatment significantly rescued the phenomenon.
  
  
  CONCLUSIONS
  These results suggest that insulin renders diabetic rats resistant to acute ischemic stroke by arresting NO reaction with superoxide to form peroxynitrite.
authors.forename: Li-Man
authors.initials: LM
authors.lastname: Hung
authors.forename: Jiung-Pang
authors.initials: JP
authors.lastname: Huang
authors.forename: Jiuan-Miaw
authors.initials: JM
authors.lastname: Liao
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Yang
authors.forename: Dai-Er
authors.initials: DE
authors.lastname: Li
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
authors.affiliation: Department of Pharmacology and Institute of Medicine, Chung Shan Medical University and Department of Pharmacy, Chung Shan Medical University Hospital, No,110, Sec, 1, Jianguo N, Rd, Taichung City 402, Taiwan. sshuang@csmu.edu.tw.
authors.forename: Shiang-Suo
authors.initials: SS
authors.lastname: Huang
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide