Correction by insulin of disturbed TG-rich LP metabolism in rats with chronic renal failure

To define the role of insulin in lipid disturbances of chronic renal failure, chronically uremic rats (U+) were supplemented by continuous insulin infusion over a 35-day experimental period and compared with control ad libitum-fed rats (C) and uremic rats without insulin (U). Uremic rats were characterized by hypoinsulinemia, an increase in both circulating very low-density lipoprotein (VLDL) and their cholesterol concentration, a normal hepatic triglyceride secretion rate (TGSR) determined with triton WR 1339, and a low adipose tissue lipoprotein lipase (LPL) activity, Chronic insulin infusion at low rate (0.5 IU/24 h) to U+ rats normalized serum insulin (from 17.0 ± 0.6 mU/l in U rats to 23.4 ± 1.7 mU/l in U+ rats), serum VLDL triglycerides (from 804 ± 65 to 410 ± 36 mg/l), and serum VLDL cholesterol (from 43 ± 8 to 16 ± 3 mg/l). Hepatic TGSR decreased significantly after insulin treatment (from 0.58 ± 0.03 to 0.44 ± 0.03 μmol/min). Moreover, adipose tissue LPL was restored to normal by insulin supplementation (from 460 ± 60 to 860 ± 150 mU per total epididymal fat in U and U+ rats, respectively). Correction of the disturbed VLDL metabolism was associated with multiple actions of insulin including 1) a decrease of peripheral lipolysis, 2) a decrease of hepatic TGSR, and 3) an increase of adipose tissue LPL activity. Because cholesterol-rich VLDL are potentially atherogenic, their normalization with insulin treatment in this animal model suggest a viable area of investigation for the prevention of accelerated atherogenesis in chronic renal failure.