Effect of tetrahydrocurcumin on insulin receptor status in type 2 diabetic rats: studies on insulin binding to erythrocytes.

Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, and exhibits many of the same physiological and pharmacological activities as curcumin and, in some systems, may exert greater antioxidant activity than curcumin. Using circulating erythrocytes as the cellular mode, the insulin-binding effect of THC and curcumin was investigated. Streptozotocin (STZ)-nicotinamide-induced male Wistar rats were used as the experimental models. THC (80 mg/kg body weight) was administered orally for 45 days. The effect of THC on blood glucose, plasma insulin and insulin binding to its receptor on the cell membrane of erythrocytes were studied. Mean specific binding of insulin was significantly lowered in diabetic rats with a decrease in plasma insulin. This was due to a significant decrease in mean insulin receptors. Erythrocytes from diabetic rats showed a decreased ability for insulin-receptor binding when compared with THC-treated diabetic rats. Scatchard analysis demonstrated that the decrease in insulin binding was accounted for by a decrease in insulin receptor sites per cell, with erythrocytes of diabetic rats having less insulin receptor sites per cell than THC-treated rats. High affinity (K d1), low affinity (K d2) and kinetic analyses revealed an increase in the average receptor affinity of erythrocytes from THC-treated rats compared with those of diabetic rats. These results suggest that acute alteration of the insulin receptor on the membranes of erythrocytes occurred in diabetic rats. Treatment with THC significantly improved specific insulin binding to the receptors, with receptor numbers and affinity binding reaching near-normal levels. Our study suggests the mechanism by which THC increases the number of total cellular insulin binding sites resulting in a significant increase in plasma insulin. The effect of THC is more prominent than that of curcumin.

Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

In the present study, the effect of succinic acid monoethyl ester (EMS) on the pattern of lipids and lipoproteins in streptozotocin-nicotinamide induced type 2 diabetes was investigated. Type 2 diabetes was induced in male Wistar rats by single intraperitoneal injection (i.p.) of 45 mg/kg streptozotocin, 15 min after the i.p administration of 110 mg/kg body weight of nicotinamide. The carboxylic nutrient EMS was administered intraperitonially at a dose of 8 micromol/g body weight for 30 days. At the end of experimental period, the effect of EMS on plasma glucose, insulin, thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP) and serum triglycerides (TG), phospholipids (PL), free fatty acids (FFA), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the percentage of antiatherogenic index (AAI) (ratio of HDL-C to total cholesterol) were studied. Administration of EMS to diabetic rats resulted in a significant reduction in the elevated levels of plasma glucose, TBARS and hydroperoxides as well as TG, PL, FFA, TC,VLDL-C and LDC-C levels. The decreased plasma insulin and serum HDL-C and percentage of AAI in diabetic rats were also reversed towards near normal. The effect produced by EMS was compared with metformin, a reference drug. The results indicates that the administration of EMS and metformin to nicotinamide-streptozotocin diabetic rats normalized plasma glucose, insulin concentrations and caused marked improvement in altered lipids, lipoprotein and lipid peroxidation markers during diabetes. Our results show the antihyperlipidemic properties of EMS and metformin in addition to its antidiabetic action. Moreover, the antihyperlipidemic effect could represent a protective mechanism against the development of atherosclerosis.