Experimental Atherosclerosis-Like Lesions Induced by Hyperinsulinism in Wistar Rats

Abstract

To elucidate the possible role of hyperinsulinism in the etiology of diabetic macroangiopathy, we studied the long-term effects of insulin injection on the arterial wall of the rat both biochemically and histologically. Fifty male Wistar rats were divided into two groups. One group was subjected to daily injection of insulin-zinc suspension (20 U/kg), and the other group was treated with saline. After 1 yr, all the animals were killed, and the lipid contents in the intimal media of their aortas were determined. Parts of the ascending aortic tissues were further examined by use of either light or electron microscopy. The triglyceride content of the insulin-treated rat aortas was significantly (P less than .05) increased compared with that of the saline-treated rat aortas. As determined by light microscopy, the intimas of the aortas from the insulin-treated rats were significantly (P less than .001) thickened, and the subendothelial tissues consisted of eosinophilic fiber bundles, amorphous ground substances, and irregularly arranged cells. These cells were identified by electron microscopy as having smooth muscle cell origin. All these findings suggest that atherosclerosis-like lesions could be induced by long-term insulin injection in the aortas of the rat and that hyperinsulinism plays a certain role in the development of diabetic macroangiopathy.

Effects of Balloon Injury on Neointimal Hyperplasia in Streptozotocin-Induced Diabetes and in Hyperinsulinemic Nondiabetic Pancreatic Islet–Transplanted Rats

“…1 Moreover, atherosclerosis-like lesions were documented when long-term insulin injections were performed in rats. 26 In addition, the intensive treatment of diabetes with insulin was not associated with a reduction in the occurrence of coronary artery disease in either the DCCT trial 27 or the UKPDS Study. 28 In many NIDDM patients, insulin levels are higher than those in nondiabetic subjects.…”

Thiazolidinedione insulin sensitizers and the heart: a tale of two organs?

“…The theoretical drawback of treating type 2 diabetes with exogenous insulin, based on its property as a potent growth‐factor which might result in increased muscularity of the arterial wall [60], did not translate into increased risk of a cardiovascular event or mortality in the UKPDS [39]. However, neither is there substantive evidence that long‐term insulin therapy reduces these outcomes in patients with type 2 diabetes, even though life‐saving benefits have been reported for insulin infusions to address hyperglycaemia in critically ill patients [61] and, when followed by intensive subcutaneous insulin therapy, to reduce 1‐year mortality after an MI in patients with diabetes [62].…”

Reducing cardiovascular disease risk in patients with type 2 diabetes and concomitant macrovascular disease: can insulin be too much of a good thing?

“…Unfortunately, only few studies have investigated pro‐atherosclerotic effects of exogenous insulin using animal models. In non‐diabetic animal models, it has been shown that long‐term insulin injections increased aortic lipid content with subsequent increased intima thickening [60,61], whereas oral insulin administration and euglycaemic/hyperinsulinaemic infusion decreased atherosclerotic lesion size [62,63]. In diabetic dogs, daily insulin infusion into femoral arteries increased artery tissue cholesterol and fatty acid content, suggesting a detrimental role for insulin in atherosclerosis during insulin resistance [64].…”