The Investigation of the Role Secretogranin 3 in the Development of Insulin Resistance and the Related Mechanisms

Autophagy plays an important role in the life cycle of the cells and it degrades the damaged organelle and then provided for the cell growth. In addition, autophagy is not only important in embryonic develoment, but also provuded mechanisms for the treatment of diabetes and cancers. Secretogranin 3 (SCG3) has an important correlation with obesity, and it is also a novel biomarker for several cancers, including lung cancer and hepatoma. A recent study indicated that SCG3 ERK1/2 pathway to stimulate angiogenesis, and related to diabetic retinopathy. In our research, we found that SCG3 abundantly accumulated in the autophagosome in the palmitate-induced insulin resistance hepatocyte model. Although numerous evidence indicated that SCG3 might play a role in the development of insulin resistance, related reports are still scarced. According to the previous studies and our research, we speculated that SCG3 might play an important pathophysiological role in diabetes and insulin resistance. Thus, in the first year of this project, we plan to enroll subjects with different glycemic status, including normal glucose tolerance, impaired glucose tolerance, impaired fasting plasma glucose and newly diagnosed diabetes to evaluate the concentrations of SCG3 in blood. In addition, we will overexpressed hepatic SCG3, using a lenti-viral vector to evaluate the impact of SCG3 in insulin sensitivity and glucose tolerance. In the second year, we will not only continue to collect clinical samples, HepG2 cell model will be used to investigate the effects of SCG3 on glucose metabolism and autophagy. In the third year, we will use logistic regression model to investigate the relationship among SCG3, insulin resistance, and the risk factors of metabolism. In addition, we will use experimental animals to investigate the impact of hepatic SCG3 deletion in high fat diet-induced diabetic mice. We expected that we can provide the evidence for the important role of SCG3 in the development of insulin resistance and the clinical application value for the diagnosis of different glycemic status.