Comparison of the effect of hyperinsulinemia on acyl-CoA:cholesterol acyltransferase activity in the liver and intestine of the rat.
Recent studies have suggested that cholesteryl ester synthesis plays a critical role in the assembly of VLDL apo B and triacylglycerol in the liver. Chronic hyperinsulinemia is associated with increased TG production and since cholesteryl ester synthesis depends on acyl CoA:cholesterol acyltransferase (ACAT), we investigated the possibility that chronic hyperinsulinemia might increase ACAT activity. We also measured ACAT activity in the intestinal mucosa, where it has been suggested to play a role in induction of diabetes-associated hypercholesterolemia. Chronically hyperinsulinemic rats were produced by injecting insulin (2 weeks, 6U/day). To prevent profound hypoglycemia, these rats were given 10% sucrose in place of drinking water. Acute hyperinsulinemia was produced by injecting a single dose of 0.5 U insulin ip. Chronic hyperinsulinemia led to a significant increase in free cholesterol, cholesteryl esters, triacylglycerols and phospholipids in the whole liver (27%, P < 0.05; 60%, P < 0.05; 70%, P < 0.01; 37%, P < 0.01, respectively) and an increase in hepatic microsomal triacylglycerol (P < 0.05). In contrast, the microsomal lipids of the intestinal mucosa decreased significantly. In chronically hyperinsulinemic rats there was no change in hepatic ACAT, while ACAT in the intestine actually decreased (26%-50%, P < 0.01).


CONCLUSIONS
since the effect of chronic hyperinsulinemia on hepatic ACAT did not parallel that seen previously on VLDL secretion, the effect of chronic hyperinsulinemia on VLDL production cannot be explained by its effect on hepatic ACAT. However, chronic hyperinsulinemia was associated with reduced ACAT activity in the intestine and this might result in decreased lipoprotein production in the hyperinsulinemic intestine.
Yang
L Y
LY
Department of Medicine and Physiology, University of Toronto, ON, Canada.
Kuksis
A
A
Steiner
G
G
D000818:Animals; D015243:Cholesterol, VLDL / Q000378:metabolism; D006946:Hyperinsulinism / Q000201:enzymology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007422:Intestines / Q000201:enzymology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D002785:Sterol O-Acyltransferase / Q000378:metabolism*
D015243:Cholesterol, VLDL; D007328:Insulin; D008055:Lipids; D002785:Sterol O-Acyltransferase