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Original Articles

Crucial Role of Aldose Reductase Activity and Plasma Glucose Level in Sorbitol Accumulation in Erythrocytes From Diabetic Patients

  1. Yoji Hamada,
  2. Ryuzo Kitoh and
  3. Philip Raskin
  1. Department of Internal Medicine, The University of Texas Southwestern Medical Center Dallas, Texas
  1. Address correspondence and reprint requests to Philip Raskin, MD, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, G5.222, Dallas, TX 75235–8858.
Diabetes 1991 Oct; 40(10): 1233-1240. https://doi.org/10.2337/diab.40.10.1233
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Abstract

Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of aldose reductase, the enzyme that converts glucose to sorbitol. In this study, we isolated aldose reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte aldose reductase was increased in diabetic patients compared with control subjects (28.1 ± 1.4 vs. 22.4 ± 1.7 nmol · min−1 · g−1 Hb, P < 0.05), but there was an ∼ threefold variation in aldose reductase activity among diabetic patients. Erythrocyte aldose reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P < 0.005 and r = 0.63, P < 0.005, respectively). The sorbitol level was higher in patients with high aldose reductase activity than in those who had low enzyme activity for any given level of glycemia. The sorbitol production rate calculated from Km and Vmax values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P < 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of aldose reductase activity by plasma glucose level (r = 0.70, P < 0.005). We conclude that both aldose reductase activity and the ambient plasma glucose concentration are important determinants of the level of sorbitol that accumulates in tissues of diabetic patients.

  • Received September 24, 1990.
  • Revision received April 4, 1991.
  • Accepted April 4, 1991.
  • Copyright © 1991 by the American Diabetes Association

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October 1991, 40(10)
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Crucial Role of Aldose Reductase Activity and Plasma Glucose Level in Sorbitol Accumulation in Erythrocytes From Diabetic Patients
Yoji Hamada, Ryuzo Kitoh, Philip Raskin
Diabetes Oct 1991, 40 (10) 1233-1240; DOI: 10.2337/diab.40.10.1233

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Crucial Role of Aldose Reductase Activity and Plasma Glucose Level in Sorbitol Accumulation in Erythrocytes From Diabetic Patients
Yoji Hamada, Ryuzo Kitoh, Philip Raskin
Diabetes Oct 1991, 40 (10) 1233-1240; DOI: 10.2337/diab.40.10.1233
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