title: Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats.
abstract: OBJECTIVE
  The renal medullary region is particularly vulnerable to reduced oxygen concentration because of its low blood perfusion and high basal oxygen consumption. This study investigated renal metabolic changes in relation to the previously observed decreased oxygen tension in streptozotocin-induced diabetic rats.
  
  
  METHODS
  Blood perfusion, oxygen tension and consumption, interstitial pH, and glycolytic and purine-based metabolites were determined in the renal cortex and the medulla of non-diabetic and diabetic animals by, respectively, laser Doppler flowmetry, oxygen and pH microelectrodes, and microdialysis. The importance of increased polyol pathway activity for the observed alterations was investigated by daily treatment with the aldose reductase inhibitor AL-1576 throughout the course of diabetes.
  
  
  RESULTS
  The diabetes-induced decrease in renal oxygen tension, due to augmented oxygen consumption, did not result in manifest hypoxia in either the cortical or the medullary region, as evaluated by microdialysis measurements of purine-based metabolites. The profound alterations in medullary oxygen metabolism were, however, associated with an increased lactate : pyruvate ratio and a concomitantly decreased pH. Notably, the renal medullary changes in oxygen tension, oxygen consumption, lactate : pyruvate ratio and pH were preventable by inhibition of aldose reductase.
  
  
  CONCLUSIONS
  Substantial metabolic changes were observed in the renal medulla in diabetic animals. These disturbances seemed to be mediated by increased polyol pathway activity and could be prevented by inhibition of aldose reductase.
authors.affiliation: Department of Medical Cell Biology, Biomedical Center, Uppsala University, Box 571, 751 23, Uppsala, Sweden. Fredrik.Palm@medcellbiol.uu.se.|Department of Diagnostic Radiology, Uppsala University, Sweden. Fredrik.Palm@medcellbiol.uu.se.
authors.forename: F
authors.initials: F
authors.lastname: Palm
authors.affiliation: Department of Medical Cell Biology, Biomedical Center, Uppsala University, Box 571, 751 23, Uppsala, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hansell
authors.affiliation: Department of Clinical Chemistry, Uppsala University, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Ronquist
authors.affiliation: Department of Cardiology, Umeå Hospital, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Waldenström
authors.affiliation: Department of Diagnostic Radiology, Uppsala University, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Liss
authors.affiliation: Department of Medical Cell Biology, Biomedical Center, Uppsala University, Box 571, 751 23, Uppsala, Sweden.|Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: P-O
authors.initials: PO
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007679:Kidney Medulla / Q000000981:diagnostic imaging / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D010101:Oxygen Consumption; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF; D012016:Reference Values; D012079:Renal Circulation; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose; D011108:Polymers; C024617:polyol