ABSTRACT
To investigate the antidiabetic effect of isopulegol in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Animals were made diabetic by feeding HFD for 4 weeks followed by single intraperitoneal injection of STZ (35 mg/kg b.w.; 0.1 M citrate buffer; pH 4.0). Plasma insulin, haemoglobin and glycogen content were decreased while increased glucose and glycated haemoglobin were observed in diabetic rats. An increase in glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenol pyruvate carboxykinase with a decrease in hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase activities was observed in diabetic rats. The expression of cyclic response element binding protein (CREB) was increased in the hepatic tissue of diabetic rats. Isopulegol dose dependently (50, 100 and 200 mg/kg b.w.) improved insulin secretion, glucose tolerance and decreased glucose levels in diabetic-treated rats. At the effective dose of 100 mg/kg b.w., isopulegol restored the activities of metabolic enzymes and down-regulated CREB expression. Thus, isopulegol restored glucose homeostasis through its insulinotrophic property.
Subject(s)
Blood Glucose/analysis , Carbohydrate Metabolism/drug effects , Cyclohexane Monoterpenes/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , Liver/enzymology , Streptozocin/toxicity , Animals , Antibiotics, Antineoplastic/toxicity , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Experimental/pathology , Fructose-Bisphosphatase/metabolism , Glucose-6-Phosphatase/metabolism , Hexokinase/metabolism , Hypoglycemic Agents/pharmacology , Insulin/blood , Male , Rats , Rats, WistarABSTRACT
BACKGROUND: Oxidative and endoplasmic reticulum stresses contribute to the pathogenesis of ß-cell dysfunction in diabetes mellitus. This study investigates the effect of isopulegol on the above stresses in HFD/STZ induced diabetic rats. METHODS: Animals in group I and II were placed in normal pellet diet and group II was treated with isopulegol at 200 mg/kg b.w. Animals in groups III-V were placed in HFD for 4 weeks and made diabetic with single intraperitoneal injection of STZ (35 mg/kg b.w) in 0.1 M citrate buffer (pH 4.5). Group III served as diabetic control while animals in group IV and V were treated with isopulegol (100 mg/kg b.w) and metformin (25 mg/kg b.w) respectively for 28 d. RESULTS: The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione sulphur transferase (GST), glutathione reductase (GR) and the levels of vitamin-E, vitamin-C, reduced glutathione (GSH) were significantly (p <0.05) decreased in plasma and tissues of diabetic rats. Thiobarbituric acid reactive acid substances (TBARS) and lipid hydroperoxides (LHP), indices of lipid peroxidation were also significantly (p <0.05) increased in diabetic rats. In pancreatic tissue ER stress markers PERK, elf2α, ATF4 and in hepatic tissue oxidative stress marker UCP-2 expression was significantly (p <1.0) increased in diabetic rats. Administration of isopulegol significantly improved antioxidant status and decreased oxidative and ER stress markers in diabetic treated rats. Histopathological studies on liver and kidney supported the above findings. The results are comparable with the standard drug metformin. CONCLUSIONS: Isopulegol a naturally occurring monoterpene alcohol attenuated oxidative and ER stress in HFD/STZ induced diabetic rats.
