Mechanism of anti-diabetic action, efficacy and safety profile of GII purified from fenugreek (Trigonella foenum-graceum Linn.) seeds in diabetic animals.

Mechanism of action of GII (100 mg/kg body weight, po for 15 days) purified from fenugreek (T. foenum-graecum) seeds was studied in the sub-diabetic and moderately diabetic rabbits. In the sub-diabetic rabbits it did not change much the content of total lipids, glycogen and proteins in the liver, muscle and heart (glycogen was not studied in the heart). However, in the moderately diabetic rabbits same treatment decreased total lipids more in the liver (21%) than those in the heart and muscle. Total protein content increased (14%) in the liver but negligible change (5-7%) was observed in heart and muscle. Glycogen increased (17%) in the liver but not in the muscle of the moderately diabetic rabbits (glycogen was not estimated in the heart). Among the enzymes of glycolysis, activity of glucokinase was not affected in the liver of both the sub-diabetic and moderately diabetic rabbits. Phosphofructokinase and pyruvate kinase activity in both sub-diabetic and moderately diabetic rabbits increased (13-50%) indicating stimulation of glycolysis. The activity of gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-diphosphatase of the sub-diabetic rabbits decreased in the liver (15-20%) but not in the kidneys. In the moderately diabetic rabbits after treatment with GII, glucokinase in the liver was not affected much (-9%) but increased well in the muscle (40%). Phosphofructokinase and pyruvate kinase were moderately increased both in the liver and the muscle (18-23%). The gluconeogenic enzyme glucose-6-phosphatase decreased reasonably well in the liver and kidneys (22, 32%). Fructose-1,6-diphosphatase decreased only slightly (10, 9%) in the moderately diabetic rabbits. Thus GII seems to decrease lipid content of liver and stimulate the enzymes of glycolysis (except glucokinase) and inhibit enzymes of gluconeogenesis in the liver of the diabetic especially moderately diabetic rabbits.