Microvascular Contributions to Insulin Resistance

Abstract

The notion that type 2 diabetes and insulin resistance are associated with many macro- and microvascular defects (1,2) is unquestionable, but whether vascular defects precede and contribute to insulin resistance is less certain and has been a controversial topic. The most compelling evidence for a vascular involvement in insulin resistance has been in skeletal muscle (3), but recent research has also implicated its involvement in adipose tissue (4), which may then lead to whole body insulin resistance via inflammation (5). The suggestion that the vasculature may be a potent contributor to insulin resistance in muscle came from early, indirect clinical studies in which insulin resistance was inversely associated with skeletal muscle capillary density in Pima Indians (6) and from studies of total blood flow during euglycemic-hyperinsulinemic clamps in normal and insulin-resistant subjects (7). Many subsequent studies by various research groups have reported corroborating data that vascular defects (especially in the microvasculature) can contribute to insulin resistance in muscle (rev. in 3 and reference list therein). The underlying consequence of the vascular defect is impaired delivery of insulin and/or glucose to the skeletal myocyte, which leads to insulin resistance. Because the muscle myocyte (and other tissues) also exhibit defects in insulin signaling and responsiveness in established states of obesity, hypertension, and diabetes (all of which are associated with insulin resistance), the significance of a vascular contribution is often questioned or undervalued. In the current issue of Diabetes , Bonner et al. (8) report data on the effects …