Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), P.O. Box 5800, 6202 AZ, Maastricht, the Netherlands.
Rev Endocr Metab Disord. 2013 Mar;14(1):29-38. doi: 10.1007/s11154-012-9231-7.
The prevalence of type 2 diabetes mellitus (T2DM) and its major risk factor, obesity, has reached epidemic proportions in Western society. How obesity leads to insulin resistance and subsequent T2DM is incompletely understood. It has been established that insulin can redirect blood flow in skeletal muscle from non-nutritive to nutritive capillary networks, without increasing total blood flow. This results in a net increase of the overall number of perfused nutritive capillary networks and thereby increases insulin-mediated glucose uptake by skeletal muscle. This process, referred to as functional (nutritive) capillary recruitment, has been shown to be endothelium-dependent and to require activation of the phosphatidylinositol-kinase (PI3K) pathway in the endothelial cell. Several studies have demonstrated that these processes are impaired in states of microvascular dysfunction. In obesity, changes in several adipokines are likely candidates to influence insulin signaling pathways in endothelial cells, thereby causing microvascular dysfunction. Microvascular dysfunction, in turn, impairs the timely access of glucose and insulin to their target tissues, and may therefore be an additional cause of insulin resistance. Thus, microvascular dysfunction may be a key feature in the development of obesity-related insulin resistance. In the present review, we will discuss the evidence for this emerging role for the microcirculation as a possible link between obesity and insulin resistance.
2 型糖尿病（T2DM）及其主要危险因素肥胖在西方社会已达到流行程度。肥胖如何导致胰岛素抵抗和随后的 T2DM 尚不完全清楚。已经确定胰岛素可以将骨骼肌中的血流从非营养性重新引导到营养性毛细血管网络，而不会增加总血流量。这导致整体灌注营养毛细血管网络的数量净增加，从而增加了骨骼肌中胰岛素介导的葡萄糖摄取。这个过程被称为功能性（营养性）毛细血管募集，已被证明依赖于内皮细胞中的磷脂酰肌醇-激酶（PI3K）途径的激活。几项研究表明，在微血管功能障碍的情况下，几种脂肪因子的变化可能会影响内皮细胞中的胰岛素信号通路，从而导致微血管功能障碍。微血管功能障碍反过来又会损害葡萄糖和胰岛素及时进入靶组织的能力，因此可能是胰岛素抵抗的另一个原因。因此，微血管功能障碍可能是肥胖相关胰岛素抵抗发展的一个关键特征。在本综述中，我们将讨论作为肥胖和胰岛素抵抗之间可能联系的微循环的这种新作用的证据。
