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 < .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 < .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.

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