Mechanism of Accumulation of Remnant Lipoproteins in Diabetes Mellitus

Abstract

In order to assess the mechanism of accumulation of remnant lipoproteins in diabetes mellitus, we examined the lipoprotein metabolism in streptozotocin-induced diabetic rats. Cholesterol-fed diabetic rats showed a marked hyperlipoproteinemia associated with an elevation of chylomicrons and remnant lipoproteins. In VLDL fraction of the cholesterol-fed diabetic rats apolipoprotein E (apo E) was increased and apo A-I, which is absent from normal VLDL, was present. This might suggest the increase of chylomicron remnants in choles-terol-fed diabetics, indicating the impairment of exogenous cholesterol pathway in diabetes. When these animals were treated with a pharmacological dose of estrogen or triiodothyronine (T₃), elevated remnants were cleared from plasma. Apo E was decreased in VLDL and HDL fractions by these treatments. We, furthermore, measured postheparin lipolytic activity. Lipoprotein lipase (LPL) activity was increased in cholesterol-fed diabetics, although hepatic lipase (HL) activity was not changed. When estrogen or T₃ was injected to these rats, LPL and HL activities were suppressed. Therefore, the clearance of remnant lipoproteins by estrogen or T₃ was not due to activition of lipolysis. The binding activity of hepatic lipoprotein receptor was also measured. The activity was enhanced by estrogen treatment in diabetics as well as in normal rats. However, there was no difference between the binding activity of hepatic receptor in diabetics and that in non-diabetics.
These data suggest that the chylomicron remnant accumulation was not due to inactivation of lipolysis. But we speculate at least in part an impaired interaction of remnant lipoproteins and hepatic receptor might contribute to the remnant lipoprotein accumulation.