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Biological and Pharmaceutical Bulletin 1996-Dec

Suppression of hyperlipidemia-associated cataracts in diabetic rats with the lipoprotein lipase activator NO-1886.

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K Tsutsumi
Y Inoue
C Yoshida

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Abstracto

Diabetic cataracts are thought to be caused by hyperglycemia associated with disturbed glucose metabolism. Diabetes mellitus often involves abnormal lipid metabolism in addition to abnormal glucose metabolism. To date, however, very few studies have counted hyperlipidemia as a risk factor for diabetic cataracts. The present study was undertaken to determine whether this actually is a risk factor for diabetic cataracts and to confirm that the onset of cataracts associated with diabetes mellitus can be suppressed by correction of hyperlipidemia. When rats with streptozotocin (STZ)-induced diabetes mellitus were fed an ordinary diet, cataracts became evident at 9 weeks in 26.7% of animals, and increased to an incidence of 73.3% after 10 weeks of STZ treatment. However, in rats with STZ-induced diabetes mellitus that were fed a cholesterol rich diet to induce severe hyperlipidemia, cataracts were observed one week earlier, after 8 weeks of treatment, in 36.0% of animals, with an increase to a 52.0% incidence and a 76.0% incidence after 9 and 10 weeks of STZ treatment, respectively. Hyperlipidemia was therefore associated with an earlier onset and an elevated incidence of diabetic cataracts. When the lipoprotein lipase (LPL) activator NO-1886 was administered to diabetic rats which had developed severe hyperlipidemia, they showed a decrease in plasma total cholesterol, triglyceride and non-high density lipoprotein (non-HDL)-cholesterol levels and an increase in high density lipoprotein (HDL)-cholesterol level, and the onset of diabetic cataracts was markedly suppressed. The results of this study suggest that hyperlipidemia and low HDL-cholesterol levels may be risk factors for the onset of diabetic cataracts, and that this onset can be suppressed if measures are taken to alleviate these risk factors. The LPL activator NO-1886 may be useful in preventing the onset of diabetic cataracts.

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