The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Abstract

Skeletal muscle is a major metabolic organ that plays a critical role in regulating glucose homeostasis and lipid utilization. Impaired muscle metabolic response is evident in diseases such as diabetes, obesity and cardiovascular diseases, and is also often associated with microvascular dysfunction. Here, we investigate the changes that can occur in the muscle microvasculature and the profound impact they can have on metabolism. Under basal conditions, vasoactive compounds are able to affect metabolism in muscle by providing more glucose and oxygen to resting muscle. Insulin and exercise increase the perfusion of muscle, and thus provide more microvascular surface area, increasing the delivery of these metabolites to muscle. Endothelial dysfunction can therefore impair the delivery of oxygen, glucose and hormones to muscle, both through effects on blood flow distribution and the transport of these factors across the endothelium, leading to a decrease in oxygen consumption and glucose metabolism. Obesity and diabetes are associated with endothelial dysfunction and are accompanied by underlying changes in metabolism and reductions in insulin sensitivity. The muscle is a highly metabolic organ, and the vasculature is essential to maintain appropriate metabolic response; therefore, the muscle microcirculation may be a target for treating metabolic disease.

Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion

“…In agreement, genetic or pharmacological inhibition of microvascular perfusion impaired insulin-stimulated muscle glucose uptake by 40% in otherwise healthy mice [38]. In addition, insulin-stimulated microvascular perfusion is reduced in different insulin-resistant conditions, including obesity and type 2 diabetes [64,65]. In cancer, impaired microvascular perfusion could be caused by elevated circulating fatty acid levels, as experimentally elevated circulating fatty acids reduced insulin-stimulated muscle microvascular perfusion by 40% [66,67] without causing impairments in intracellular insulin signaling in healthy humans [17].…”