IS THE HYPERTRIGLYCERIDEMIA ASSOCIATED WITH INSULIN DEFICIENCY CAUSED BY DECREASED LIPOPROTEIN-LIPASE ACTIVITY

Questions have been raised as to whether reduced lipoprotein lipase (LPL) activity can account for the defect in plasma removal of very low density lipoprotein (VLDL) associated with insulin deficiency. In order to study this issue, streptozotocin-induced insulin deficiency was produced in 2-mo-old rats. Three groups of rats were studied: control, moderate diabetes (glucose>200<350 mg/dl), and severe diabetes (glucose>350 mg/dl). One week later food was withdrawn at 8 a.m., and the following measurements made at 2 p.m. (6 H after removal of food): (1) plasma glucose, insulin, and triglyceride (TG) levels; (2) VLDL-TG secretion rate; and (3) adipose tissue and skeletal muscle LPL activity. Rats with moderate diabetes had higher glucose and lower insulin levels than did control rats, and these differences were accentuated in rats with severe diabetes. Plasma TG levels were elevated (P<0.001) in rats with moderate (↑99%) and severe diabetes (↑126%) and this was associated with a fall (P<0.001) in VLDL-TG secretion. An increase in plasma TG levels, despite a decrease in VLDL-TG secretion, indicates the presence of a profound defect in VLDL-TG removal from plasma. However, muscle LPL of rats with severe diabetes and moderate diabetes was equal to that of control rats, and adipose tissue LPL was only moderately (P<0.05) reduced (MD= ↓25% SD= ↓32%). These results indicate that plasma TG levels rise in young, insulin-deficient rats as a result of a defect in removal of VLDL-TG from plasma. This removal defect is associated with normal muscle and only moderately reduced adipose tissue LPL activity, suggesting that the VLDL-TG removal defect associated with insulin deficiency may not be a simple function of a decrease in total (muscle + adipose tissue) LPL activity.