As a biochemist and molecular biologist, I have a long-standing research interest in the structure and function of biologically important proteins and their roles in human diseases. My focus in the past twelve years has been on Ncb5or (NADH cytochrome b5 oxidoreductase). This is a novel redox enzyme associated with pathogenesis of lean diabetes. The human Ncb5or gene is linked to lean diabetes, and the Ncb5or knockout mice develop early onset lean diabetes by age 7 weeks due to beta-cell dysfunction and death.
Our recent findings show that Ncb5or deficiency in beta-cells leads to profound changes in lipid and iron metabolism, increased oxidative and ER stress, and lipotoxicity similar to that observed in animals with systemic lipid overload. Thus, our Ncb5or-null mouse represents a novel monogenic diabetes model. My lab is currently studying the role of Ncb5or in iron homeostasis and mitochondrial function and their relation to lipid metabolism in beta-cells and other cell types.
One key finding in Ncb5or knockout mice is that they lose fat early in development. This phenomenon is interesting since children diagnosed with type 1 diabetes often lose fat and stop growing as an early indication of the onset of disease. By studying the role of Ncb5or in fat loss and beta cell destruction, we hope to more fully understand the early phases of type 1 diabetes.
Obesity is linked to type 2 diabetes, and both are major human health issues that are expected to worsen in coming decades. Recent research has shown that adipose tissue is the body’s largest endocrine unit, not merely inert energy storage as previously thought. Triglyceride-rich lipid droplets in adipocytes are depleted in Ncb5or knockout mice. With increased knowledge about Ncb5or’s biological function in triglyceride synthesis and energy homeostasis, we may be able to develop therapeutic drugs to combat obesity.
This work is supported by the National Institutes of Health and the School of Health Professions at KU Medical Center. Learn more about the project.
For more information, please contact:
Hao Zhu, PhD, Diabetes Research Group
2146 W. 39th Avenue
Kansas City, KS 66160