While ovariectomy significantly enhanced the reduction of p-AMPK protein levels in the left ventricle of female T2D animals (OVX+T2D vs. T2D, P ≤ 0.05), treatment with the GPER agonist G-1 significantly reversed the attenuation of p-AMPK levels in the left ventricle of these animals (OVX+T2D+G-1 vs. OVX+T2D+Veh, P ≤ 0.05). The gene discussed is GPER1; the disease is type 2 diabetes mellitus.