To investigate the cardioprotective effect of GCGR mAb and its possible mechanism, CMECs were isolated from db/m mice, db/db mice and GCGR mAb‐treated db/db mice, and tandem mass tag (TMT)‐based quantitative proteomic analysis was used to identify the proteomic signature of CMECs associated with the development and amelioration of diabetic cardiomyopathy. The gene discussed is GCGR; the disease is diabetic cardiomyopathy.