Ruan Hong, Pownall Henry J
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane West, Piscataway, NJ 08854, USA.
Curr Opin Investig Drugs. 2009 Apr;10(4):346-52.
Insulin suppresses the release of non-esterified fatty acids from adipocytes and suppresses glucose production from hepatocytes, but stimulates glucose uptake by skeletal muscle, liver and adipose tissue. Insulin resistance, the failure of an ample supply of insulin to mediate these effects, is an early and fundamental defect in type 2 diabetes (T2D) associated with obesity. Adipose tissue not only acts as an energy depot, but also secretes a variety of endocrine, paracrine and autocrine factors, which regulate energy metabolism and insulin activity. In addition, adipose tissue from obese individuals has a distinct secretory profile that alters both adipocyte function and overall in vivo insulin sensitivity. Obesity is coupled to insulin resistance and diabetes through the action of adipose-derived factors, in a process that involves intricate signaling pathways and transcriptional regulators in various cell types of adipose tissue, in addition to cross-talk between adipose and non-adipose tissues. Thus, the dissection of the specific pathways that contribute to insulin resistance in obese individuals is a crucial component in understanding obesity-linked T2D. In this review, recent in vitro and in vivo data that implicate the IKK (inhibitor of kappaB kinase)/NFkappaB pathway, a component of both fatty acid and inflammatory cytokine signaling cascades, in the regulation of insulin sensitivity are discussed, and the value of this pathway as a therapeutic target in T2D is evaluated.
胰岛素可抑制脂肪细胞中非酯化脂肪酸的释放，抑制肝细胞中葡萄糖的生成，但会刺激骨骼肌、肝脏和脂肪组织对葡萄糖的摄取。胰岛素抵抗是指充足的胰岛素无法介导这些作用，它是2型糖尿病（T2D）与肥胖相关的早期且基本的缺陷。脂肪组织不仅作为能量储存库，还分泌多种内分泌、旁分泌和自分泌因子，这些因子调节能量代谢和胰岛素活性。此外，肥胖个体的脂肪组织具有独特的分泌特征，会改变脂肪细胞功能和整体体内胰岛素敏感性。肥胖通过脂肪衍生因子的作用与胰岛素抵抗和糖尿病相关联，这一过程涉及脂肪组织各种细胞类型中复杂的信号通路和转录调节因子，以及脂肪组织与非脂肪组织之间的相互作用。因此，剖析导致肥胖个体胰岛素抵抗的特定途径是理解肥胖相关T2D的关键组成部分。在本综述中，讨论了近期体外和体内数据，这些数据表明IKK（κB激酶抑制剂）/NFκB途径（脂肪酸和炎性细胞因子信号级联反应的一个组成部分）参与胰岛素敏感性的调节，并评估了该途径作为T2D治疗靶点的价值。
