Abstract：
The incidence of obesity is rapidly increasing worldwide. Obesity-associated insulin resistance has long been established as a significant risk factor for obesity-related disorders such as type 2 diabetes and atherosclerosis. Insulin plays a key role in systemic glucose metabolism, with the liver, skeletal muscle, and adipose tissue as the major acting tissues. Insulin receptors and the downstream insulin signaling-related molecules are expressed in various tissues, including vascular endothelial cells, vascular smooth muscle cells, and monocytes/macrophages. In obesity, decreased insulin action is considered a driver for associated disorders. However, whether insulin action has a positive or negative effect on obesity-related disorders depends on the tissue in which it acts. While an enhancement of insulin signaling in the liver increases hepatic fat accumulation and exacerbates dyslipidemia, enhancement of insulin signaling in adipose tissue protects against obesity-related dysfunction of various organs by increasing the capacity for fat accumulation in the adipose tissue and inhibiting ectopic fat accumulation. Thus, this \"healthy adipose tissue expansion\" by enhancing insulin sensitivity in adipose tissue, but not in the liver, may be an effective therapeutic strategy for obesity-related disorders. To effectively address obesity-related metabolic disorders, the mechanisms of insulin resistance in various tissues of obese patients must be understood and drugs that enhance insulin action must be developed. In this article, we review the potential of interventions that enhance insulin signaling as a therapeutic strategy for obesity-related disorders, focusing on the molecular mechanisms of insulin action in each tissue.
摘要：
肥胖症的发病率在世界范围内迅速增加。长期以来，肥胖相关的胰岛素抵抗已被确定为肥胖相关疾病如2型糖尿病和动脉粥样硬化的重要危险因素。胰岛素在全身葡萄糖代谢中起关键作用，肝脏，骨骼肌,和脂肪组织作为主要作用组织。胰岛素受体和下游胰岛素信号相关分子在各种组织中表达，包括血管内皮细胞,血管平滑肌细胞，和单核细胞/巨噬细胞。在肥胖症中，胰岛素作用降低被认为是相关疾病的驱动因素。然而,胰岛素的作用对肥胖相关疾病有正面还是负面的影响取决于它所作用的组织.虽然肝脏中胰岛素信号的增强会增加肝脏脂肪积累并加剧血脂异常，脂肪组织中胰岛素信号的增强通过增加脂肪组织中脂肪积累的能力和抑制异位脂肪积累来防止各种器官的肥胖相关功能障碍。因此，这种“健康的脂肪组织扩张”通过增强脂肪组织中的胰岛素敏感性，但不是在肝脏，可能是肥胖相关疾病的有效治疗策略。为了有效解决肥胖相关的代谢紊乱，必须了解肥胖患者各种组织中胰岛素抵抗的机制，并开发增强胰岛素作用的药物。在这篇文章中,我们回顾了增强胰岛素信号的干预措施作为肥胖相关疾病治疗策略的潜力。关注胰岛素在每个组织中作用的分子机制。
