Role of insulin in regulation of high density lipoprotein metabolism.

The effect of alloxan-induced insulin deficiency on high density lipoprotein (HDL) metabolism was studied in rabbits. Rabbits with alloxan-induced diabetes had significantly higher (P less than 0.001, mean +/- SEM) plasma concentrations of glucose (541 +/- 13 vs. 130 +/- 2 mg/dl), triglyceride (2851 +/- 332 vs. 101 +/- 10 mg/dl), and total plasma cholesterol (228 +/- 55 vs. 42 +/- 4 mg/dl) than did normal control rabbits. However, diabetic rabbits had lower plasma HDL-cholesterol (7.2 +/- 1 vs. 51.3 +/- 1.3 mg/dl, P less than 0.001) and HDL apoA-I (38.3 +/- 6.0 vs. 87.2 +/- 4.3 mg/dl, P less than 0.001) concentrations. HDL kinetics were compared in diabetic and normal rabbits, using either 125I-labeled HDL or HDL labeled with 125I-labeled apoA-I, and it was demonstrated that HDL fractional catabolic rate (FCR) was slower and residence time was longer in the diabetic rabbits when either tracer was used. The slow FCR and the low apoA-I pool size led to reduced apoA-I/HDL synthetic rate in diabetic rabbits (0.97 +/- 0.11 vs. 0.34 +/- 0.07 mg per kg per hr). Thus, the reduced plasma HDL-cholesterol concentrations seen in rabbits with alloxan-induced insulin deficiency was associated with a lower total apoA-I/HDL synthetic rate. Since insulin treatment restored to normal all of the changes in plasma lipoprotein concentration and kinetics seen in diabetic rabbits, it is unlikely that the phenomena observed were secondary to a nonspecific toxic effect of alloxan. These data strongly support the view that insulin plays an important role in regulation of HDL metabolism.