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 mumol/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 suggests a viable area of investigation for the prevention of accelerated atherogenesis in chronic renal failure.
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D015243:Cholesterol, VLDL; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D010743:Phospholipids / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood*; D014511:Uremia / Q000097:blood
D001053:Apolipoproteins; D001786:Blood Glucose; D015243:Cholesterol, VLDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D008079:Lipoproteins, VLDL; D010743:Phospholipids; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D019344:Lactic Acid; D002784:Cholesterol; D008071:Lipoprotein Lipase