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Diabetologia. 2004 Jul;47(7):1223-1231. doi: 10.1007/s00125-004-1434-3. Epub 2004 Jun 30.

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats.

Author information

1
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Box 571, 751 23, Uppsala, Sweden. Fredrik.Palm@medcellbiol.uu.se.
2
Department of Diagnostic Radiology, Uppsala University, Sweden. Fredrik.Palm@medcellbiol.uu.se.
3
Department of Medical Cell Biology, Biomedical Center, Uppsala University, Box 571, 751 23, Uppsala, Sweden.
4
Department of Clinical Chemistry, Uppsala University, Sweden.
5
Department of Cardiology, Umeå Hospital, Umeå, Sweden.
6
Department of Diagnostic Radiology, Uppsala University, Sweden.
7
Department of Medical Sciences, Uppsala University, Sweden.

Abstract

AIMS/HYPOTHESIS:

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/INTERPRETATION:

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.

PMID:
15232683
DOI:
10.1007/s00125-004-1434-3
[Indexed for MEDLINE]

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