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Gluconeogenesis control and consequently glucose output from the liver furthermore partially enhanced liver and muscle insulin sensitivity results in the stimulation of the insulin/AKT-2 signaling pathway which indirectly restored glucose homeostasis in the treated T2DM group. Our therapeutic nanoformulation also improved glycogen storage in the liver and membrane translocation of GLUT4 in the muscle of the treated T2DM group. In conclusion, GPR8PCK-1siRNA (3 mg/Kg BW) restored glucose homeostasis by controlling the hepatic glucose pro