Why does experimental insulin deficiency lead to a decrease in removal of very low density-triglyceride from plasma?

Abstract

We have previously suggested that mechanisms other than reduced lipoprotein lipase (LPL) activity might contribute to the defect in plasma removal of very low density lipoprotein (VLDL)-triglyceride (TG) observed in insulin-deficient rats. To further evaluate this phenomenon, removal rates of TG in nonfractionated plasma, as well as in isolated lipoprotein fractions obtained from insulin-deficient and control rats, were compared in a new, sensitive in vivo bioassay system (estradiol-treated male rats with a consistently low endogenous VLDL-TG pool). Removal of TG in nonfractionated plasma from insulin-deficient rats was slower than that of control rats: 3.0 +/- 0.3 vs 1.6 +/- 0.2 min (P less than 0.001). No difference was found in removal rate of isolated VLDL-TG (2.5 +/- 0.3 vs 2.6 +/- 0.4 min), or in removal rates of TG carried in other lipoprotein fractions. We next determined the effect of injection into normal rats of aliquots of dialyzed lipoprotein-free (D greater than 1.215) plasma from insulin-deficient and control rats on the removal rate of normal VLDL-TG, and found that lipoprotein-free plasma from insulin-deficient rats significantly (P less than 0.01) prolonged removal of normal VLDL-TG (4.3 +/- 0.4 to 6.8 +/- 0.7 min). This same fraction did not interfere with the in vitro hydrolysis of normal VLDL-TG by post-heparin LPL. Thus, a factor in the D greater than 1.215 plasma fraction of insulin-deficient rats is present which interferes with the rate of removal of TG from plasma, unrelated to inhibition of LPL activity.