Hyperglycemia in normotriglyceridemic, hypercholesterolemic insulin-treated diabetic rabbits does not accelerate...

Severely hyperlipidemic alloxan-diabetic cholesterol-fed rabbits were treated with different daily doses of insulin in order to study the effect of insulin on plasma lipids, lipoproteins and postheparin lipoprotein lipase activity. At plasma triglyceride levels of 15,000 mg/dl, untreated diabetic rabbits carried 73% (1950 mg/dl) of plasma total cholesterol in lipoproteins with a diameter larger than 75 nm (Sf greater than 400), 25% in smaller very low density lipoproteins (VLDL) and 1% in both low and high density lipoproteins (LDL, HDL). Insulin treatment greatly reduced plasma total cholesterol and triglyceride concentrations. The decrease of plasma total cholesterol concentration was paralleled by a decrease in the cholesterol of the largest lipoproteins (Sf greater than 400) and an increase in cholesterol of both smaller very low density lipoproteins and low density lipoproteins. At the same time, postheparin plasma lipoprotein lipase activity increased 2-8-fold. When plasma triglyceride levels were normalized by insulin treatment, the lipoprotein cholesterol distribution in diabetic cholesterol-fed rabbits was similar to that of normal cholesterol-fed rabbits. To study development of atherosclerosis, diabetic rabbits were cholesterol-fed and treated with insulin for eight weeks such that the triglyceride levels were normalized, but plasma glucose levels were still greatly elevated. Nondiabetic rabbits were cholesterol-fed simultaneously. Plasma cholesterol and triglyceride levels were similar in the two groups of rabbits, as well as cholesterol in Sf greater than 400 or smaller VLDL and cholesterol in HDL. However, LDL-cholesterol concentration in the insulin-treated diabetic rabbits was 1.5-2 times that in the nondiabetic rabbits. The two groups of rabbits developed similar degrees of atherosclerosis, as judged by aortic cholesterol content. Apparently, partially controlled diabetes in cholesterol-fed rabbits does not accelerate atherogenesis beyond that observed in nondiabetic cholesterol-fed rabbits.