Kanzaki M, Pessin J E
Department of Physiology & Biophysics, The University of Iowa, Iowa City 52242, USA.
Cell Biochem Biophys. 2001;35(2):191-209. doi: 10.1385/CBB:35:2:191.
Insulin is a potent metabolic hormone essential for the maintenance of normal circulating blood glucose level in mammals. The physiologic control of glucose homeostasis results from a balance between hepatic glucose release (glycogenolysis and gluconeogenesis) and dietary glucose absorption versus skeletal muscle and adipose tissue glucose uptake and disposal. Disruption of this delicate balance either through defects in insulin secretion, liver glucose output, or peripheral tissue glucose uptake results in pathophysiological states of insulin resistance and diabetes. In particular, glucose transport into skeletal muscle and adipose tissue is the rate-limiting step in glucose metabolism and reduction in the efficiency of this process (insulin resistance) is one of the earliest predictors for the development of Type II diabetes. Importantly, recent studies have directly implicated an impairment in insulin receptor signal transduction as the prime mechanism for peripheral tissue insulin resistance. In this review, we have focused on recent developments in our understanding of the molecular mechanisms and signal transduction pathways that insulin utilizes to specifically regulate glucose uptake. The detailed understanding of these events will provide a conceptual framework for the development of new therapeutic targets to treat this chronic and debilitating disease process.
胰岛素是一种重要的代谢激素，对维持哺乳动物正常的循环血糖水平至关重要。葡萄糖稳态的生理控制源于肝脏葡萄糖释放（糖原分解和糖异生）与饮食中葡萄糖吸收之间的平衡，以及骨骼肌和脂肪组织对葡萄糖的摄取与处理之间的平衡。通过胰岛素分泌缺陷、肝脏葡萄糖输出或外周组织葡萄糖摄取等方式破坏这种微妙的平衡，会导致胰岛素抵抗和糖尿病等病理生理状态。特别是，葡萄糖转运至骨骼肌和脂肪组织是葡萄糖代谢中的限速步骤，而这一过程效率的降低（胰岛素抵抗）是II型糖尿病发展的最早预测指标之一。重要的是，最近的研究直接表明胰岛素受体信号转导受损是外周组织胰岛素抵抗的主要机制。在本综述中，我们重点关注了我们对胰岛素用于特异性调节葡萄糖摄取的分子机制和信号转导途径的最新认识进展。对这些事件的详细理解将为开发治疗这种慢性衰弱性疾病的新治疗靶点提供一个概念框架。
