HYPERINSULINEMIA ACCELERATES ACCUMULATION OF CHOLESTEROL ESTER IN AORTA OF RATS WITH TRANSPLANTED PANCREAS

Hyperinsulinaemia may play a role in the development of atherosclerosi s; however, the direct effect of endogenous insulin on the atheroscler otic process is not well understood. To clarify this situation we perf ormed pancreas transplantation with systemic venous drainage in Wistar Shionogi (WS) and Spontaneous Hypertensive (SHR) rats. Both rats rece ived syngeneic pancreaticoduodenal transplants from donor rats. SHR ra ts were used to observe the additive effects of both hypertension and hyperinsulinaemia on the atherosclerotic process. Peak brood insulin l evels after a glucose load were approximately two limes higher in tran splanted rats than in nontransplanted WS and SHR rats, By contrast, th ere was no difference in plasma glucose responses between transplanted and non-transplanted rats. Hyperinsulinaemia was not related to dysli pidaemia and hypertension in transplanted rats. Nine months after tran splantation, the cholesterol ester contents of the aortas of both WS a nd SHR transplanted rats were significantly higher than in the control rats (WS: 1.9 +/- 1.0 vs 3.8 +/- 2.1 mg/g dry tissue, p < 0.01; SHR: 1.7 +/- 1.3 vs 3.7 +/- 1.4 mg/g dry tissue, p < 0.05). No differences were demonstrated in the thickness of the intima or in the histology o f the aortas of transplanted and control rats. To study the mechanism for cholesterol ester accumulation in the arterial wall, we measured n eutral cholesterol ester hydrolase activities in vascular medial smoot h muscle cells. Insulin significantly suppressed neutral cholesterol e ster hydrolase activities in medial smooth muscle cells. Our results i ndicate that endogenous hyperinsulinaemia contributes to the developme nt of atherosclerosis by accelerating cholesterol ester accumulation i n the arterial wall.