Our results showed that, in early diabetic rats, p-AMPKα was significantly increased which was induced by either diabetes or diabetes with I/R and that the increase of cardiac mTOR in diabetes was not sufficient to combat p-AMPKα to stimulate autophagy, and this led to excessive autophagy as reflected by significant increases in the ratio of LC3 II/I and protein P62 expression and exacerbated postischemic I/RI. The gene discussed is MTOR; the disease is diabetes mellitus.