Hyperinsulinaemia accelerates accumulation of cholesterol ester in aorta of rats with transplanted pancreas

Abstract

Hyperinsulinaemia may play a role in the development of atherosclerosis; however, the direct effect of endogenous insulin on the atherosclerotic process is not well understood. To clarify this situation we performed pancreas transplantation with systemic venous drainage in Wistar Shionogi (WS) and Spontaneous Hypertensive (SHR) rats. Both rats received syngeneic pancreaticoduodenal transplants from donor rats. SHR rats were used to observe the additive effects of both hypertension and hyperinsulinaemia on the atherosclerotic process. Peak blood insulin levels after a glucose load were approximately two times higher in transplanted rats than in non-transplanted WS and SHR rats. By contrast, there was no difference in plasma glucose responses between transplanted and non-transplanted rats. Hyperinsulinaemia was not related to dyslipidaemia and hypertension in transplanted rats. Nine months after transplantation, the cholesterol ester contents of the aortas of both WS and 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 of the aortas of transplanted and control rats. To study the mechanism for cholesterol ester accumulation in the arterial wall, we measured neutral cholesterol ester hydrolase activities in vascular medial smooth muscle cells. Insulin significantly suppressed neutral cholesterol ester hydrolase activities in medial smooth muscle cells. Our results indicate that endogenous hyperinsulinaemia contributes to the development of atherosclerosis by accelerating cholesterol ester accumulation in the arterial wall.