Inhibition of sorbitol dehydrogenase

Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats

Ronald Tilton, K. Chang, J. R. Nyengaard, M. Van den Enden, Y. Ido, J. R. Williamson

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N- dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S- 0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.

Original languageEnglish (US)
Pages (from-to)234-242
Number of pages9
JournalDiabetes
Volume44
Issue number2
StatePublished - 1995
Externally publishedYes

Fingerprint

S 0773
L-Iditol 2-Dehydrogenase
Sorbitol
Streptozocin
Blood Vessels
Sciatic Nerve
Fructose
Peripheral Nerves
Aorta
Neural Pathways
Aldehyde Reductase
Experimental Diabetes Mellitus
Neural Conduction
Glycosylated Hemoglobin A
Pyruvic Acid
Drinking Water
Oxidation-Reduction
Retina
Lactic Acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Tilton, R., Chang, K., Nyengaard, J. R., Van den Enden, M., Ido, Y., & Williamson, J. R. (1995). Inhibition of sorbitol dehydrogenase: Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. Diabetes, 44(2), 234-242.

Inhibition of sorbitol dehydrogenase : Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. / Tilton, Ronald; Chang, K.; Nyengaard, J. R.; Van den Enden, M.; Ido, Y.; Williamson, J. R.

In: Diabetes, Vol. 44, No. 2, 1995, p. 234-242.

Research output: Contribution to journalArticle

Tilton, R, Chang, K, Nyengaard, JR, Van den Enden, M, Ido, Y & Williamson, JR 1995, 'Inhibition of sorbitol dehydrogenase: Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats', Diabetes, vol. 44, no. 2, pp. 234-242.
Tilton R, Chang K, Nyengaard JR, Van den Enden M, Ido Y, Williamson JR. Inhibition of sorbitol dehydrogenase: Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. Diabetes. 1995;44(2):234-242.
Tilton, Ronald ; Chang, K. ; Nyengaard, J. R. ; Van den Enden, M. ; Ido, Y. ; Williamson, J. R. / Inhibition of sorbitol dehydrogenase : Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats. In: Diabetes. 1995 ; Vol. 44, No. 2. pp. 234-242.
@article{af35b29e2f9f4b4a95c770f764fd39bf,
title = "Inhibition of sorbitol dehydrogenase: Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats",
abstract = "These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N- dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S- 0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.",
author = "Ronald Tilton and K. Chang and Nyengaard, {J. R.} and {Van den Enden}, M. and Y. Ido and Williamson, {J. R.}",
year = "1995",
language = "English (US)",
volume = "44",
pages = "234--242",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "2",

}

TY - JOUR

T1 - Inhibition of sorbitol dehydrogenase

T2 - Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats

AU - Tilton, Ronald

AU - Chang, K.

AU - Nyengaard, J. R.

AU - Van den Enden, M.

AU - Ido, Y.

AU - Williamson, J. R.

PY - 1995

Y1 - 1995

N2 - These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N- dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S- 0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.

AB - These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N- dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S- 0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.

UR - http://www.scopus.com/inward/record.url?scp=0028966139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028966139&partnerID=8YFLogxK

M3 - Article

VL - 44

SP - 234

EP - 242

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -