胰岛素抵抗与心力衰竭发病密切相关，治疗心衰同时改善胰岛素抵抗成为心衰治疗新策略。β肾上腺素受体（βAR）阻滞剂作为心衰常规治疗药物，因疗效和不良反应个体差异较大以及选择性βAR阻滞剂加重胰岛素抵抗的作用，在糖尿病心力衰竭患者应用极为受限。前期研究表明非选择性βAR阻滞剂卡维地洛在改善糖尿病心功能不全同时改善胰岛素抵抗，而预实验发现胰岛素通过β2AR激活Akt，促葡萄糖转运体GLUT4转运及葡萄糖摄取，结合卡维地洛是反向β2AR激动剂，推测卡维地洛可偏向激活β2AR-βarrestin2-Akt信号通路促进胰岛素调控GLUT4转运。阐明胰岛素依赖于β2AR促GLUT4转运调控葡萄糖摄取的作用机制，及其在卡维地洛改善胰岛素抵抗中的作用，明确不同βAR阻滞剂对胰岛素抵抗和心力衰竭的影响，将为胰岛素调控葡萄糖转运的作用机制提供新的理论，并为合理选用βAR阻滞剂治疗糖尿病心力衰竭提供新思路和策略。

Heart failure (HF) is associated with insulin resistance (IR) which can drive the chronic stimulation of Insulin signaling, meanwhile, cardiac IR can develop in congestive HF. It is important to ameliorate HF and IR together. Although β-blockers are effective in HF treatment, β-blockers are limited to be used in diabetes associated with HF due to worsening IR in HF by selective β1 blockers. However, non-selective β-blocker carvedilol improves both of the cardiac dysfunction and IR in diabetes associated HF. Our preliminary data shows that insulin induces Akt phosphorylation and GLUT4 translocation mediated glucose uptake in β2AR dependent manner. As carvedilol is a biased β2AR agonist, we hypothesize that carvedilol prompts insulin induced glucose uptake via activation of β2AR-β-arrestin2-Akt signaling pathway. In this proposal, we aim to characterize the mechanism underlying insulin induces GLUT4 translocation in β2AR dependent manner. Successful characterizing the effect of carvedilol on insulin resistance in HF will helps to gain insight on the influence of β2AR dependent insulin induced GLUT4 translocation on the therapeutic effects of different β-blockers in IR and HF.