On December 26, Dr. Chen Zheng of the University of Michigan made an academic report to students and researchers at the Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS) on the role TRAF molecules play in liver metabolism. Zheng previously found that some members of the TRAF family of molecules are quite highly expressed in liver tissue among those with diabetes, and that they can combine with the insulin receptor substrate (IRS), causing IRS ubiquitination, leading to insulin resistance.
Though diabetes is more often found among people in North America and Europe as well as more developed regions of Asia including Japan, South Korea and Hong Kong, recent data shows that China is beginning to see a rise in the disease, affecting some 11% of mainland China’s population. Increasingly unhealthy diets and increasingly sedentary lifestyles among urban dwellers in China have contributed to a rise in obesity—a major factor in diabetes—another perhaps more significant component is growing insulin resistance, Nearly two decades of research suggests that obesity causes chronic inflammation of liver tissue via insulin resistance.
The traditional theory underpinning this relationship holds that weight gain during the course of obesity induces low grade chronic inflammation of certain tissues in the liver, leading to the release of pro-inflammatory cytokines such as TNF into circulation, which inhibits the activities of insulin by stimulating the activation of JNK and IKK signaling pathways, which in turn inhibit insulin. JNK activation leads to inhibitory serine phosphorylation of insulin receptor substrate (IRS) proteins inhibiting insulin signaling, thereby causing insulin resistance and ultimately leading to the developing of type 2 diabetes. Zheng, however, presented a new mechanism that may help better explain this process, wherein TRAFs mediated through IRS cause insulin resistance ubiquitination.
At the University of Michigan, Zheng current research is based around examining adenoviral vectors and tissue-specific knockout mouse studies as a means of TRAFs family regulate hepatic glucose metabolism mechanisms. His research has recently been published in Diabetes, FASEB journal, Nature Medicine, Circulation Research, Cardiovascular Research, JBC as well as other prestigious medical journals.