Diabetes mellitus is a metabolic disorder characterized by glucose intolerance. Although the advent of insulin therapy extended the lives of many diabetic patients, the management of diabetes-associated complications poses a significant economic burden to developed as well as developing countries. While a number of mechanisms have been proposed to account for the pathogenesis of the long-term complications, the impairment in antioxidant defense appears to be a common manifestation....[ Read more ]

Diabetes mellitus is a metabolic disorder characterized by glucose intolerance. Although the advent of insulin therapy extended the lives of many diabetic patients, the management of diabetes-associated complications poses a significant economic burden to developed as well as developing countries. While a number of mechanisms have been proposed to account for the pathogenesis of the long-term complications, the impairment in antioxidant defense appears to be a common manifestation.

In the study of 15-week streptozotocin-induced diabetic rats, total glutathione level was decreased in the liver and increased in the heart, kidney and plasma. Insulin treatment could completely or partially restore almost all diabetes-associated changes in tissue antioxidant status, except the decreased hepatic glutathione S-transferases (GST) activities. The results suggest that the diabetes-induced alterations in tissue glutathione antioxidant system may possibly reflect an inter-organ antioxidant response to a generalized increase in tissue oxidative stress. Also, the diabetes-associated impairment in hepatic GST activities may have implication in the susceptibility of diabetic liver to hepatotoxins.

In this connection, the study on short-term (2 weeks) diabetes in rats revealed the markedly increased susceptibility to carbon tetrachloride (CCl₄)-induced hepatotoxicity, which was associated with an impairment in glutathione antioxidant response. Hepatic reduced glutathione (GSH) level in short-term diabetic rats was increased while that of the liver mitochondria was decreased. When CCl₄ was administered at a dose of 0.2 ml/kg, diabetic rats exhibited an increased extent of hepatocellular damage compared with their non-diabetic counterparts. Such damage could be protected completely by insulin treatment and partially by schisandrin B (Sch B) pretreatment. The protection afforded by insulin and Sch B pretreatment may at least in part be attributed to the restoration of hepatic ascorbic acid level and GSWGSSG ratio, as well as the enhancement of both cytosolic and microsomal GST activities.