Insulin resistance mediated biochemical alterations in eye lens of neonatal streptozotocin-induced diabetic rat

Abstract

Cataract, the leading cause of blindness worldwide, is associated with many risk factors including diabetes. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) states are associated with pre-diabetes and insulin resistance. This condition subsequently leads to the development of type-2 diabetes. Epidemiological studies indicated that not only diabetes but IGT/IFG will also lead to the development of microvascular disorders and cataract. However, there are no studies on the mechanism of insulin resistance induced changes in the eye lens. In the present study, IGT/IFG-induced changes in lens using neonatal-streptozotocin (nSTZ) rat model have been investigated. Though, nSTZ rats showed the signs of IGT and insulin resistance starting from two months old, they did not develop cataract even at the age of 8-months. However, biochemical analysis indicates a three-fold increase in sorbitol levels in nSTZ lens upon prolonged (6-months) IGT and insulin resistance. Also there was an increase in lipid peroxidation and alterations in antioxidant enzymes. Results of this study showed that activation of polyol pathway and increased oxidative stress, commonly associated with long-term complications of diabetes, have been observed in eye lens due to prolonged IGT and insulin resistance which may lead to cataract.