The effect of insulin on the incorporation of sodium (1-14C)-acetate into the lipids of the rat aorta

Abstract

Experiments were performed to test the hypothesis that insulin has a role in the pathogenesis of atherosclerosis. Rats were injected intravenously with sodium (1-1aC)-acetate (10 ~Ci per 100 g weight) with and without insulin (100000 ~ units per 100 g weight). After one hour, they were killed, and the lipids extracted from the cleaned aortas. The lipids were separated by thin layer chromatography, and the radioactivity in the total lipids and the lipid fractions was measured. The results showed that insulin stimulated the incorporation of sodium (1-14C)-aeetate into total lipids, cholesterol and phospholipids to a significant extent. Incorporation into triglyceride just failed to reach statistical significance. These results are compatible with some of the features of human atherosclerosis, and support the hypothesis that insulin and atheroma are causally linked. The finding that insulin had an effect on cholesterol metabolism was unexpected and warrants further investigation.

Responsiveness to insulin of glucose metabolism in cultured rat and human arterial smooth muscle cells.

“…Thus, the glucose transport into the arterial smooth muscle cells of both species may possibly be insulin independent. Our results on the rat cells were essentially similar to those of Urrutia et al (1962) and different from those of Stout (1971Stout ( , 1975. No immediate effect of insulin on glucose metabolism was found in the aortic tissue of the rabbit (Mulcahy and Winegrad 1962) or the pig (Somer and Schwartz 1976).…”

“…Similar results were obtained in the in vitro experiment on rabbit aortic tissue by Mulcahy and Winegrad (1962), and on pig aortic tissue by Somer and Schwartz (1976). On the contrary, Stout (1971Stout ( , 1975 reported a significant acceleration of lipid synthesis by aorta in vivo within a few hr after insulin injection in the rat. Although the reason for the discrepancy between the above authors could not be clarified, the in vitro and in vivo studies may well yield the different results.…”

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

“…Insulin promotes de novo lipogenesis and augments hepatic VLDL synthesis [22, 23] via its stimulation of sterol regulatory-element-binding protein-1c and its inhibition of acetyl-CoA carboxylase [24]. In cultured arterial smooth muscle cells, insulin augmented LDL-cholesterol transport [25]. Insulin is a potent growth factor, augments collagen synthesis [26, 27], stimulates arterial smooth muscle cell proliferation [28, 29] and turns on multiple genes involved in inflammation [27].…”

Glucose intolerance, diabetes mellitus and atherosclerosis; prospects for prevention

“…Beyond a certain point, the failing insulin response breaks down completely and subnormal insulin levels occur. Both of these response phases may favour atherogenesis; hyperinsulinaemia will increase the production of triglyceride-rich lipoprotein (Reaven et al, 1967), will inhibit tissue lipolysis and stimulate in situ lipogenesis (Stout, 1971). Insulin may also have a direct stimulatory effect (Stout, Bierman and Ross, 1975) on the proliferation and perhaps other metabolic activity of the smooth muscle cells of the arterial media which may invade the intima and contribute to the focal lipid accumulations which culminate in the atheromatous plaque (Ross and Glomset, 1973).…”