胰岛素抵抗是引起糖尿病、高血压、肥胖症和心血管疾病的共同病理生理基础。β-arrestin2是具有多重调节作用的效应分子，β-arrestin2表达缺陷可引起IR，但对其在IR和T2DM中的生物学功能了解非常有限，其参与的主要信号通路和精确的调控机制还不十分清楚。我们采用慢病毒载体作为实现β-arrestin2基因过表达或缺陷表达的手段，将β-arrestin2 或RNAi慢病毒载体转入普食或高脂喂养的C57BL/6及AopE-/-小鼠体内，利用扩展的胰岛素钳夹技术评价该模型的胰岛素敏感性和糖脂代谢变化，观察其潜在的外周生物学效应和信号传导机制。并且在细胞模型中高表达或抑制β-arrestin2基因，从体外、体内两个水平阐明β-arrestin2在IR和T2DM中调控糖脂代谢的作用机制和规律，为寻找IR和T2DM发生的分子生物学靶点提供新的实验依据和理论基础。

Metabolic syndrome related diseases such as type 2 diabetes (T2DM), hyperlipidemia, hypertension and coronary heart disease (CHD) have become major public health problems in most industrialized countries. Insulin resistance (IR), an important feature of metabolic diseases, serves as a common pathophysiological basis shared by T2DM, hyperlipemia, hypertension and CHD. β-arrestin2 is a multifunctional signaling adaptor. Deficiency of a β-arrestin2 signal complex contributes to IR. But the biological functions of β-arrestin2 in IR and T2DM are limited, and the major signaling pathways and the exact mechanism is not clear. In this study, we constructed recombinant lentivirus vectors carrying β-arrestin2 gene or siRNA fragment of β-arrestin2 to bidirectional regulative the expression of β-arrestin2 both in a normal diet or high fat feeding C57BL/6 and AopE-/- mice. Then we used euglycaemic-hyperinsulinaemic clamp to evaluate insulin sensitivity and metabolism changes in this animal model and further observing the potential biological effect and molecular mechanism of signal transduction. We also over-expressed or defective-expressed β-arrestin2 in Hepa1-6 and 3T3-L1 cells to further clarify the regulation of glucose-lipid metabolism and potential mechanism in IR and T2DM through β-arrestin2 both in vitro and in vivo. These results may provide new experimental and theoretical basis for searching target molecules of IR and T2DM.