Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

•Systemic treatment of an antibody-based glucagon receptor antagonist confers cardioprotection against myocardial infarction and post-myocardial infarction remodeling in mice.•Systemic treatment of glucagon receptor antagonist prevents pressure overload induced cardiac remodeling and dysfunction in mice.•Glucagon receptor antagonist treatment attenuates the pathological progression of heart failure induced by pressure overload in mice.•Long-term suppression of glucagon signaling is potentially an effective therapy for heart failure with different etiologies independent of metabolic disorders.