High glucose increased smooth muscle cell glucose metabolism through the citric acid cycle and pentose phosphate pathway by 240% and 90%, respectively, but did not directly stimulate proliferation.
Does diabetes and hyperglycemia accelerate smooth muscle cell accumulation and proliferation in atherosclerotic lesions?
Diabetes accelerates smooth muscle cell accumulation in atherosclerotic lesions, likely mediated by secondary effects of the hyperglycemic state rather than direct glucose stimulation.
In combination with other factors, hyperglycemia may cause the accelerated progression of atherosclerosis in people with diabetes. Arterial smooth muscle cell (SMC) proliferation and accumulation contribute to formation of advanced atherosclerotic lesions. Therefore, we investigated the effects of hyperglycemia on SMC proliferation and accumulation in vivo and in isolated arteries and SMCs by taking advantage of a new porcine model of diabetes-accelerated atherosclerosis, in which diabetic animals are hyperglycemic without receiving exogenous insulin. We show that diabetic animals fed a cholesterol-rich diet, like humans, develop severe lesions of atherosclerosis characterized by SMC accumulation and proliferation, whereas lesions in nondiabetic animals contain fewer SMCs after 20 weeks. However, high glucose (25 mmol/l) does not directly stimulate the proliferation of SMCs in isolated arterial tissue from diabetic or nondiabetic animals, or of cultured SMCs from these animals or from humans. Furthermore, the mitogenic actions of platelet-derived growth factor, IGF-I, or serum are not enhanced by high glucose. High glucose increases SMC glucose metabolism through the citric acid cycle and the pentose phosphate pathway by 240 and 90%, respectively, but <10% of consumed glucose is metabolized through these pathways. Instead, most of the consumed glucose is converted into lactate and secreted by the SMCs. Thus, diabetes markedly accelerates SMC proliferation and accumulation in atherosclerotic lesions. The stimulatory effect of diabetes on SMCs is likely to be mediated by effects secondary to the hyperglycemic state.
Suzuki et al. (Sun,) conducted a other in Atherosclerosis. Hyperglycemia vs. Normoglycemia was evaluated on Smooth muscle cell proliferation and accumulation. High glucose increased smooth muscle cell glucose metabolism through the citric acid cycle and pentose phosphate pathway by 240% and 90%, respectively, but did not directly stimulate proliferation.