Daily administration of 200 mg/kg metformin concurrently with 1mg/kg RAPA i.p. for 6 successive days before induction of ischemia and promptly at the onset of reperfusion to rats raised the stimulatory effect of metformin on eNOS (Fig. 7), HO-1 (Fig. 9), CSE (Fig. 10), and Beclin-1 (Fig. 11) protein expressions in the liver tissue. The gene discussed is HMOX1; the disease is ischemia.