Fang X, Sweeney G
Department of Biology, York University, Toronto, ON, Canada M3J 1P3.
Biochem Soc Trans. 2006 Nov;34(Pt 5):798-801. doi: 10.1042/BST0340798.
Nutritional control of molecular events has become of great interest given the increased incidence of diet-induced obesity, and consequently Type 2 (non-insulin-dependent) diabetes, in recent years. The altered adipose tissue content in obese individuals results in an altered profile of circulating adipokines, and here we focus on adiponectin, whose circulating levels decrease in obese individuals. Adiponectin is a 30 kDa protein but circulates primarily as hexameric, oligomeric and, to a lesser extent, trimeric forms. Full-length adiponectin can also be cleaved to produce a fragment containing the globular domain that exerts potent metabolic effects. Adiponectin has insulin-mimetic and -sensitizing actions including stimulation of glucose uptake in skeletal muscle and suppression of glucose production in liver. Hence, adiponectin has attracted great interest as an antidiabetic agent. Adiponectin acts via two receptor isoforms, AdipoR1 (adiponectin receptor 1) and AdipoR2, which have distinct tissue distributions and affinities for recognition of the various adiponectin forms. Expression of AdipoR isoforms can be regulated by hyperinsulinaemia and hyperglycaemia with the consequence of increased sensitivity or resistance to specific forms of adiponectin. In summary, regulation of adiponectin or AdipoR expression may be of great importance in the development of metabolic perturbations characteristic of Type 2 diabetes in obese individuals.
鉴于近年来饮食诱导的肥胖症以及随之而来的2型（非胰岛素依赖型）糖尿病发病率上升，分子事件的营养控制已引起了极大关注。肥胖个体体内脂肪组织含量的改变导致循环脂联素水平的变化，在此我们聚焦于脂联素，肥胖个体的循环脂联素水平会降低。脂联素是一种30 kDa的蛋白质，但主要以六聚体、寡聚体形式循环，三聚体形式的比例较小。全长脂联素也可被切割产生一个包含球状结构域的片段，该片段具有强大的代谢作用。脂联素具有胰岛素模拟和增敏作用，包括刺激骨骼肌摄取葡萄糖以及抑制肝脏生成葡萄糖。因此，脂联素作为一种抗糖尿病药物引起了极大关注。脂联素通过两种受体亚型AdipoR1（脂联素受体1）和AdipoR2发挥作用，它们对不同形式脂联素的识别具有不同的组织分布和亲和力。AdipoR亚型的表达可受高胰岛素血症和高血糖症调节，结果是对特定形式脂联素的敏感性增加或抵抗。总之，脂联素或AdipoR表达的调节在肥胖个体2型糖尿病特征性代谢紊乱的发生发展中可能具有重要意义。
