Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes

Deepak Chandra, Elias B. Jackson, Kota Ramana, Rocky Kelley, Satish Srivastava, Aruni Bhatnagar

Research output: Contribution to journalArticle

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Abstract

Increased glucose utilization by aldose reductase (AR) has been implicated in the development of diabetes complications. However, the mechanisms that regulate AR during diabetes remain unknown. Herein we report that several nitric oxide (NO) donors prevent ex vivo synthesis of sorbitol in erythrocytes obtained from diabetic or nondiabetic rats. Compared with erythrocytes of nondiabetic rats, the AR activity in the erythrocytes of diabetic rats was less sensitive to inhibition by NO donors or by AR inhibitors-sorbinil or tolrestat. Treatment with NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced AR activity and sorbitol accumulation in tissues of nondiabetic rats. Application of transdermal nitroglycerin patches or treatment with L-arginine did not inhibit AR activity or sorbitol accumulation in the tissues of nondiabetic animals. Treatment with L-NAME increased, whereas treatment with L-arginine or nitroglycerine patches decreased AR activity and sorbitol content in tissues of diabetic rats. These observations suggest that NO maintains AR in an inactive state and that this repression is relieved in diabetic tissues. Thus, increasing NO availability may be a useful strategy for inhibiting the polyol pathway and preventing the development of diabetes complications.

Original languageEnglish (US)
Pages (from-to)3095-3101
Number of pages7
JournalDiabetes
Volume51
Issue number10
StatePublished - Oct 1 2002

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Aldehyde Reductase
Sorbitol
Nitric Oxide
NG-Nitroarginine Methyl Ester
Nitric Oxide Donors
Erythrocytes
Nitroglycerin
Diabetes Complications
Arginine
Transdermal Patch
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chandra, D., Jackson, E. B., Ramana, K., Kelley, R., Srivastava, S., & Bhatnagar, A. (2002). Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes. Diabetes, 51(10), 3095-3101.

Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes. / Chandra, Deepak; Jackson, Elias B.; Ramana, Kota; Kelley, Rocky; Srivastava, Satish; Bhatnagar, Aruni.

In: Diabetes, Vol. 51, No. 10, 01.10.2002, p. 3095-3101.

Research output: Contribution to journalArticle

Chandra, D, Jackson, EB, Ramana, K, Kelley, R, Srivastava, S & Bhatnagar, A 2002, 'Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes', Diabetes, vol. 51, no. 10, pp. 3095-3101.
Chandra D, Jackson EB, Ramana K, Kelley R, Srivastava S, Bhatnagar A. Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes. Diabetes. 2002 Oct 1;51(10):3095-3101.
Chandra, Deepak ; Jackson, Elias B. ; Ramana, Kota ; Kelley, Rocky ; Srivastava, Satish ; Bhatnagar, Aruni. / Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes. In: Diabetes. 2002 ; Vol. 51, No. 10. pp. 3095-3101.
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