The major findings were as follows: (1) Nrg4 could alleviate DM-induced myocardial injury; (2) Nrg4 attenuated diabetic cardiomyopathy by upregulating autophagy in a type 1 diabetic mouse model; and (3) Nrg4 activated autophagy via the AMPK/mTOR-dependent signalling pathway. Here, NRG4 is linked to diabetic cardiomyopathy.