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Heart failure is the leading cause of death worldwide. Our focus is on non-genetic mechanisms by which cardiac regeneration can be lengthened or enhanced. Specifically, we are interested in the cyto-protective effects of glucose in cardiomyocyte growth, differentiation and proliferation and how this knowledge can be applied to regeneration therapies. Our preliminary data showed that glucose induces cardiomyocyte proliferation and inhibits cardiomyocyte maturation in human embryonic stem cells derived cardiomyocytes (hESC-CM) via the Pentose Phosphate Pathway in a dose dependent manner. Whether this pathway can be a therapeutic target for heart regeneration is unknown. Our hypothesis is that glucose promotes neonatal heart regeneration in a murine model. Non-Transmural cryoinjury was performed to the apex of the left ventricle in wild-type pups and cardiac specific overexpression of Glucose Transporter 1 Transgenic pups. In the acute phase (P1-P7), the level of cardiomyocyte cell proliferation was measured via flow cytometry analysis and immunostaining with PH3 and cTnnt. Glucose uptake by cardiomyocytes was measured by 18F-FDG assay and Glut1 immunostaining. In the chronic phase (P14, P21, P40), we quantified the level of fibrosis by histology (H&E and Picrosirius Red) and neovascularization by immunostaining with PECAM. Increased cardiomyocyte proliferation was observed in the Transgenic Glut1 pups. Myocardial glucose uptake declines from the muscular layer towards the trabecular layer, corresponding with maturation of the heart. We observed that Glut1 cardiomyocyte-specific overexpression resulted in improved cardiac repair compared to wild type (WT) mice at 21 days postnatally. Compared to wild-type, Glut1 hearts showed increased angiogenesis around the site of injury secondary to an increase in cardiomyocyte proliferation. This study is the first to demonstrate the potential role of glucose as a promoter for cardiac regeneration and reveal a potential mechanism for congenital cardiomyopathy associated with diabetic pregnancy.