Meal-Related Increases in Microvascular Vasomotion Are Impaired in Obese Individuals

Abstract

Obesity is associated with insulin resistance, hypertension, cardiovascular disease, and type 2 diabetes (1), but the mechanisms underlying these associations are incompletely understood. This article reviews and adds original data (i.e., in the postprandial state) to the evidence for microvascular dysfunction, including impairment of insulin-stimulated microvascular perfusion as a key element in the pathogenesis of obesity-related hypertension and insulin resistance (2,3). The microcirculation is widely taken to encompass vessels <150 μm (i.e., arterioles, capillaries, and venules) (4) and has two important functions. First, arterioles regulate hydrostatic pressure and peripheral vascular resistance (4). Importantly, dysfunction of the microcirculation, with concomitant increases in vasoconstrictor tone, will increase total peripheral resistance and, other things being equal, blood pressure, as reviewed elsewhere (2,3). Second, it regulates tissue perfusion to optimize the delivery of nutrients and removal of waste products within tissues in response to variations in demand. In this respect, insulin has been shown to play an important role (5). Insulin redirects blood flow within the muscle microvascular bed to increase available capillary surface area, an effect referred to as “capillary recruitment” (6,7). In addition, insulin induces vasodilation of resistance vessels, resulting in an increase in total muscle blood flow (8). Whether this increase in total muscle blood flow, which occurs later in time compared with the redirection of flow to nutritive capillary beds, serves to enhance insulin-mediated glucose uptake remains controversial (9). However, it has been generally accepted that capillary recruitment is crucial for the delivery of insulin and glucose to tissue. Indeed, several studies have shown that insulin-mediated increases in capillary recruitment account for approximately half of insulin-mediated muscle glucose uptake in vivo (10–14). Insulin’s effect on microvascular blood flow is, therefore, an important regulator of insulin-mediated muscle glucose uptake, the main …