This study examines the effect of an aldose reductase inhibitor (sorbinil) on the flux of specifically labeled glucose through alternative pathways of metabolism in the lens of normal and diabetic rats 1 wk after the induction of diabetes with alloxan. In the diabetic rat lens, there was an apparent increase in the flux of glucose through the pentose phosphate pathway (PPP), as measured by the difference in the yields of 14CO2 from]1-14C[glucose and [6-14C]glucose [C1–C6], this value was 0.087 ± 0.005 and 0.263 ± 0.034 μmol · g lens−1 · h (mean + SE of 6 values) for control and diabetic rats, respectively; sorbinil treatment decreased the values to 0.065 ± 0.008 and 0.171 ± 0.028, respectively. With glucose tritiated on carbon 2 or 3, it has been shown that the flux of glucose through the polyol route is increased, whereas the flux through the glycolytic pathway is decreased in the diabetic rat lens; both are restored toward normal in the sorbinil-treated diabetic group. These results suggest that the dual effects of diabetes in increasing 1) the lens content of glucose and glucose 6-phosphate and 2) the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens. The inhibition of aldose reductase by sorbinil tends to normalize the redox state of the nicotinamide nucleotides, reimposing the NADPH limitation on the PPP and increasing the availability of NAD+ for the glycolytic route.
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Original Contribution|
November 01 1986
Effect of Aldose Reductase Inhibitor (Sorbinil) on Integration of Polyol Pathway, Pentose Phosphate Pathway, and Glycolytic Route in Diabetic Rat Lens
A -M Gonzalez;
A -M Gonzalez
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School
Mortimer Street, London, UK
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M Sochor;
M Sochor
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School
Mortimer Street, London, UK
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J S Hothersall;
J S Hothersall
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School
Mortimer Street, London, UK
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P McLean
P McLean
Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School
Mortimer Street, London, UK
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Address reprint requests to Dr. Milena Sochor, Courtauld Institute of Biochemistry, The Middlesex Hospital Medical School, Mortimer Street, London W1P 7PN, UK.
1
Current address for T.U. is Section of Endocrinology, Dept. of Medicine, University of Illinois, Chicago, IL.
Diabetes 1986;35(11):1200–1205
Article history
Received:
September 26 1985
Revision Received:
May 30 1986
PubMed:
3093302
Citation
A -M Gonzalez, M Sochor, J S Hothersall, P McLean; Effect of Aldose Reductase Inhibitor (Sorbinil) on Integration of Polyol Pathway, Pentose Phosphate Pathway, and Glycolytic Route in Diabetic Rat Lens. Diabetes 1 November 1986; 35 (11): 1200–1205. https://doi.org/10.2337/diab.35.11.1200
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