Insulin-like growth factor II receptor alpha overexpression in heart aggravates hyperglycemia-induced cardiac inflammation and myocardial necrosis

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor alpha (IGF-IIR alpha) is a cardiac risk factor. In this study, we hypothesized IGF-IIR alpha could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIR alpha overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIR alpha in diabetic hearts. The results showed that IGF-IIR alpha overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIR alpha overexpression. Correspondingly, IGF-IIR alpha overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIR alpha overexpression. Overall, all results provid clear evidence that IGF-IIR alpha can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIR alpha under different stresses and its downstream regulation in the heart still require further research.