title: Hyperglycemia exacerbates and insulin fails to protect in acute renal ischemia in the rat.
abstract: Hyperglycemia worsens ischemic injury in several ischemic models. To determine whether renal lactate accumulation was associated with hyperglycemia-exacerbated postischemic renal dysfunction and mortality, halothane-anesthetized rats underwent right nephrectomy and 45 min of left renal artery and vein occlusion. Prior to ischemia, rats received saline (n = 22), glucose (2 g/kg, n = 22), or insulin (4 U/kg, n = 18). Sham-operated glucose-treated rats (2 g/kg, n = 4) underwent right nephrectomy and no vascular occlusion. As anticipated, glucose pretreatment elevated plasma glucose, while insulin pretreatment lowered plasma glucose; both were significantly different from values in saline controls. Creatinine was unchanged in sham-operated rats but was significantly higher in glucose-treated rats at 24 and 48 hr postischemia compared to saline controls. No statistical differences in creatinine were found when comparing saline controls to insulin-treated rats. Eighteen percent of glucose-treated rats survived to 72 hr postocclusion, while 45% of insulin-treated rats, 73% of saline control rats, and 100% of sham-operated rats survived this period. In a separate but identical treatment protocol, renal tissue was serially sampled and lactate content was determined in rats pretreated with saline (n = 7), glucose (n = 6) or insulin (n = 6) or sham-operated (n = 2) and receiving identical operation. Tissue lactate concentration did not change during serial sampling in the sham group. During ischemia, lactate was significantly higher in glucose-treated rats and significantly lower in insulin-treated rats as compared to saline controls. The adverse effects of exogenous glucose and attendant hyperglycemia on renal function during normothermic renal ischemia are demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
authors.forename: R M
authors.initials: RM
authors.lastname: Podrazik
authors.forename: J E
authors.initials: JE
authors.lastname: Natale
authors.forename: G B
authors.initials: GB
authors.lastname: Zelenock
authors.forename: L G
authors.initials: LG
authors.lastname: D'Alecy
mesh_terms: D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D007511:Ischemia / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007773:Lactates / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007773:Lactates