Impaired microvascular perfusion: a consequence of vascular dysfunction and a potential cause of insulin resistance in muscle

Abstract

Insulin has an exercise-like action to increase microvascular perfusion of skeletal muscle and thereby enhance delivery of hormone and nutrient to the myocytes. With insulin resistance, insulin's action to increase microvascular perfusion is markedly impaired. This review examines the present status of these observations and techniques available to measure such changes as well as the possible underpinning mechanisms. Low physiological doses of insulin and light exercise have been shown to increase microvascular perfusion without increasing bulk blood flow. In these circumstances, blood flow is proposed to be redirected from the nonnutritive route to the nutritive route with flow becoming dominant in the nonnutritive route when insulin resistance has developed. Increased vasomotion controlled by vascular smooth muscle may be part of the explanation by which insulin mediates an increase in microvascular perfusion, as seen from the effects of insulin on both muscle and skin microvascular blood flow. In addition, vascular dysfunction appears to be an early development in the onset of insulin resistance, with the consequence that impaired glucose delivery, more so than insulin delivery, accounts for the diminished glucose uptake by insulin-resistant muscle. Regular exercise may prevent and ameliorate insulin resistance by increasing "vascular fitness" and thereby recovering insulin-mediated capillary recruitment.

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

“…In addition to total limb blood flow, another mediator of insulin and AA delivery to the muscle is the distribution of blood flow between so-called nutritive and non-nutritive routes (Clark et al 2006;Clark 2008;Durham et al 2010), as reduced nutritive blood flow may contribute to the anabolic resistance observed with ageing Wilkes et al 2009). We have previously shown that in young individuals pharmacological enhancement of 'nutritive' muscle microvascular blood flow was not associated with increases in muscle protein synthesis .…”

Assessment of microvascular and metabolic responses in the skin

“…Commonly a field of about 1 mm 2 on the dorsal nail fold of a finger is studied using an optical microscope. Perfused capillaries are counted before and after a provocation, such as arterial occlusion with a finger cuff (Clark, 2008). Only the capillaries filled with RBC will be visualised, with the risk of the true number of capillaries being underestimated.…”

Endothelial dysfunction in type 2 diabetes

“…Detailed studies in experimental animal models of diabetes support this mechanism [17], whereas the evidence in humans is indirect and probably relevant to pharmacological insulin concentrations. Nevertheless, the hypothesis that endothelial dysfunction contributes to the cellular insulin resistance of obesity or hypertension, when directly tested in vivo in man [18,19], has not been confirmed.…”