Evidence for a New Cause of Defective Plasma Removal of Very Low Density Lipoproteins in Insulin-Deficient Rats

These studies were initiated to see if factors other than reduced lipoprotein lipase activity might contribute to the defect in plasma removal of very low density lipoprotein (VLDL) that is observed in insulin-deficient rats. VLDL-triglyceride (TG) was labeled in vivo with ³H-glycerol in control and diabetic rats, and ali-quots of plasma containing ³H-VLDL were injected into normal recipient rats. The half-time (t_1/2) of removal was almost twice as long when plasma from diabetic rats was injected, and this was true when the diabetic rats were fed either sucrose or regular chow. A comparable increase in t_1/2 was observed when ³H-VLDL isolated from normal rats was recombined with VLDL-free plasma from control and diabetic rats and injected into normal recipients. As before, the changes observed were not dependent upon antecedent diet. However, no significant difference in t_1/2 was observed when ³H-VLDL was isolated from control and diabetic rats and injected into normal recipients. Thus, there appears to be a factor present in VLDL-free plasma obtained from diabetic rats that interferes with removal of VLDL from the vascular compartment. Whether this factor is found in diabetic plasma in vivo, or is transferred from diabetic VLDL to diabetic plasma in the isolation procedure, remains to be clarified. In either event, there appears to be a factor, other than reduced LPL activity, that may play a role in the defect of VLDL-TG removal seen in insulin deficiency.