University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Hills Road, Cambridge CB2 OQQ, United Kingdom.
J Clin Endocrinol Metab. 2010 Apr;95(4):1544-54. doi: 10.1210/jc.2009-2286. Epub 2010 Feb 17.
Adiponectin is a highly abundant plasma protein synthesized nearly exclusively in adipose tissue from the ADIPOQ gene. It has excited intense interest because of robust correlation of its circulating levels with indices of insulin resistance (IR) and risk of type 2 diabetes, and their unusual inverse relationship with fat mass. It has been suggested that pharmacological strategies aimed at augmenting adiponectin levels or action may generate novel insulin-sensitizing drugs.
Relevant publications were identified by searching PubMed, with secondary searches of their bibliographies.
Rodent studies suggest that adiponectin exerts a direct insulin-sensitizing effect on the liver, consistent with a role in the pathogenesis of prevalent forms of IR and its sequelae. However, the complex higher-order structure of adiponectin and inconsistent reports regarding its putative receptors have complicated efforts to understand the mechanistic basis of this. No proof yet exists that adiponectin modulates insulin sensitivity in humans, and genetic, biochemical, and physiological evidence suggests that low adiponectin levels may be a consequence of IR with compensatory hyperinsulinemia. This suggests that there may be a bidirectional relationship between IR and hypoadiponectinemia in humans.
The relationship between adiponectin and insulin action in humans is more complex than often suggested. Further investigation of the direction of causality in this relationship, allied to studies of the cellular mechanisms involved, will be central to improving understanding of the physiological role of this enigmatic protein, and to efforts to exploit it for therapeutic benefit.
脂联素是一种高度丰富的血浆蛋白，几乎仅由脂肪组织中的 ADIPOQ 基因合成。由于其循环水平与胰岛素抵抗（IR）指数和 2 型糖尿病风险呈强相关，且与脂肪量呈异常负相关，因此引起了极大的兴趣。有人提出，旨在提高脂联素水平或作用的药物策略可能会产生新的胰岛素增敏药物。
通过搜索 PubMed 确定了相关出版物，并对其参考文献进行了二次搜索。
啮齿动物研究表明，脂联素对肝脏具有直接的胰岛素增敏作用，这与其在常见形式的 IR 及其后果中的作用一致。然而，脂联素复杂的高级结构和其假定受体的不一致报告使得理解其机制基础变得复杂。目前尚无证据表明脂联素可调节人类的胰岛素敏感性，遗传、生化和生理学证据表明，低脂联素水平可能是 IR 伴代偿性高胰岛素血症的结果。这表明在人类中，IR 和低脂联素血症之间可能存在双向关系。
脂联素与人类胰岛素作用之间的关系比通常所认为的更为复杂。进一步研究这种关系中的因果关系方向，以及涉及的细胞机制研究，将是理解这种神秘蛋白质生理作用的关键，并为利用其治疗益处做出努力。
