The aims of the current study were to: (1) determine the effect of hyperinsulinemia using both in vitro and in vivo approaches, on cardiac TLR4 expression in non-obese animals, and (2) investigate the impact of altered cardiac TLR4 expression during hyperinsulinemia on markers of TLR4 signaling (IL-6, TNF-α, and SOCS3) and cardiac GLUT (1, 4, 8, 12) expression. The gene discussed is SOCS3; the disease is hyperinsulinism.