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

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 diabet... Full description

Journal Title: Diabetologia 2004, Vol.47 (7), p.1223-1231
Main Author: PALM, F
Other Authors: HANSELL, P , RONQUIST, G , WALDENSTRÖM, A , LISS, P , CARLSSON, P.-O
Format: Electronic Article Electronic Article
Language: English
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Publisher: Berlin: Springer
ID: ISSN: 0012-186X
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title: Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats
format: Article
creator:
  • PALM, F
  • HANSELL, P
  • RONQUIST, G
  • WALDENSTRÖM, A
  • LISS, P
  • CARLSSON, P.-O
subjects:
  • Aldose reductase
  • Animals
  • Biological and medical sciences
  • Blood Glucose - metabolism
  • Cells
  • Diabetes
  • Diabetes Mellitus, Experimental - metabolism
  • Diabetes. Impaired glucose tolerance
  • Endocrine pancreas. Apud cells (diseases)
  • Endocrinopathies
  • Insulin
  • Kidney
  • Kidney Medulla - diagnostic imaging
  • Kidney Medulla - metabolism
  • Kidney Medulla/metabolism/ultrasonography
  • Lactates
  • Laser-Doppler Flowmetry
  • Male
  • Medical and Health Sciences
  • Medical sciences
  • MEDICIN
  • Medicin och hälsovetenskap
  • MEDICINE
  • Metabolism
  • Metabolites
  • Microcirculation
  • Monosaccharides
  • Oxygen Consumption
  • Physiological aspects
  • Polymers - metabolism
  • Polyols
  • Rats
  • Rats, Inbred WF
  • Reference Values
  • Renal Circulation
  • Streptozocin
  • Sugars
  • Ultrasonography
ispartof: Diabetologia, 2004, Vol.47 (7), p.1223-1231
description: 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. 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. 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. 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.
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
  • 1432-0428
url: Link


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titlePolyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats
creatorPALM, F ; HANSELL, P ; RONQUIST, G ; WALDENSTRÖM, A ; LISS, P ; CARLSSON, P.-O
creatorcontribPALM, F ; HANSELL, P ; RONQUIST, G ; WALDENSTRÖM, A ; LISS, P ; CARLSSON, P.-O
descriptionThe 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. 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. 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. 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.
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languageeng
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subjectAldose reductase ; Animals ; Biological and medical sciences ; Blood Glucose - metabolism ; Cells ; Diabetes ; Diabetes Mellitus, Experimental - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Insulin ; Kidney ; Kidney Medulla - diagnostic imaging ; Kidney Medulla - metabolism ; Kidney Medulla/metabolism/ultrasonography ; Lactates ; Laser-Doppler Flowmetry ; Male ; Medical and Health Sciences ; Medical sciences ; MEDICIN ; Medicin och hälsovetenskap ; MEDICINE ; Metabolism ; Metabolites ; Microcirculation ; Monosaccharides ; Oxygen Consumption ; Physiological aspects ; Polymers - metabolism ; Polyols ; Rats ; Rats, Inbred WF ; Reference Values ; Renal Circulation ; Streptozocin ; Sugars ; Ultrasonography
ispartofDiabetologia, 2004, Vol.47 (7), p.1223-1231
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1Diabetologia
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descriptionThe 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. 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. 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. 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.
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1Animals
2Biological and medical sciences
3Blood Glucose - metabolism
4Cells
5Diabetes
6Diabetes Mellitus, Experimental - metabolism
7Diabetes. Impaired glucose tolerance
8Endocrine pancreas. Apud cells (diseases)
9Endocrinopathies
10Insulin
11Kidney
12Kidney Medulla - diagnostic imaging
13Kidney Medulla - metabolism
14Kidney Medulla/metabolism/ultrasonography
15Lactates
16Laser-Doppler Flowmetry
17Male
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21Medicin och hälsovetenskap
22MEDICINE
23Metabolism
24Metabolites
25Microcirculation
26Monosaccharides
27Oxygen Consumption
28Physiological aspects
29Polymers - metabolism
30Polyols
31Rats
32Rats, Inbred WF
33Reference Values
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36Sugars
37Ultrasonography
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titlePolyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats
authorPALM, F ; HANSELL, P ; RONQUIST, G ; WALDENSTRÖM, A ; LISS, P ; CARLSSON, P.-O
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0Aldose reductase
1Animals
2Biological and medical sciences
3Blood Glucose - metabolism
4Cells
5Diabetes
6Diabetes Mellitus, Experimental - metabolism
7Diabetes. Impaired glucose tolerance
8Endocrine pancreas. Apud cells (diseases)
9Endocrinopathies
10Insulin
11Kidney
12Kidney Medulla - diagnostic imaging
13Kidney Medulla - metabolism
14Kidney Medulla/metabolism/ultrasonography
15Lactates
16Laser-Doppler Flowmetry
17Male
18Medical and Health Sciences
19Medical sciences
20MEDICIN
21Medicin och hälsovetenskap
22MEDICINE
23Metabolism
24Metabolites
25Microcirculation
26Monosaccharides
27Oxygen Consumption
28Physiological aspects
29Polymers - metabolism
30Polyols
31Rats
32Rats, Inbred WF
33Reference Values
34Renal Circulation
35Streptozocin
36Sugars
37Ultrasonography
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abstractThe 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. 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. 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. 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.
copBerlin
pubSpringer
pmid15232683
doi10.1007/s00125-004-1434-3
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