Regulation of glycogen metabolism by anti-dyslipidemic action of gemfibrozil and cholestyramine in a dyslipidemic-diabetic hamster model

摘要

Dyslipidemia with diabetes in hamsters, as a result of feeding with high-fat diet, caused accumulation of nonesterified fatty acid, increased lipolysis, and hyperglycemia, with decreased insulin activity. The lipid-lowering drag gemfibrozil improved insulin secretion and lowered the plasma glucose, plasma and tissue lipids viz., cholesterol, triglyceride, nonesterified fatty acids, and glycerol. Cholestyr-amine, a potent bile acid sequestrant was less effective than gemfibrozil in the diabetic-dyslipidemic hamster model. Treatment with the above drugs also affected glycogen metabolism by reactivation of the enzymes glycogen synthase, glucoki-nase, hexokinase, and glycogen phosphorylase, in liver and muscle, and reduced fat load by increasing faecal excretion of lipids. These drugs counteracted the insulin resistance by improving insulin secretion. Gemfibrozil was more effective than cholestyramine in controlling hyperglycemia, because the lipid-lowering action of the latter was mediated only by its bile acid sequestration activity.