H. Henry Dong, PhD

Beta-cell compensation and etiology of gestational diabetes and type 2 diabetes: 

Dr. Dong focuses on studies of the mechanisms underlying beta-cell compensation, known as an adaptive mechanism by which pancreatic beta-cells increase insulin secretion to overcome insulin resistance for maintaining normal blood sugar levels in individuals with overweight or obesity. Beta-cell compensation culminates in the expansion of beta-cell mass and upregulation of insulin synthesis and secretion. Failure of beta-cells to compensate for insulin resistance contributes to insulin insufficiency and type 2 diabetes. Likewise, beta-cell compensation ensues in women during pregnancy. Pregnancy is associated with maternal insulin resistance in the 3rd trimester during pregnancy, a physiological response that serves to spare blood glucose and nutrient supplies for the fetus. Insufficient beta-cell compensation for maternal insulin resistance is an underlying cause of gestational diabetes. To date, how beta-cells compensate for insulin resistance and what causes beta-cell failure in gestational diabetes and type 2 diabetes are poorly understood. Dr. Dong's team works to characterize genetic factors that integrate insulin resistance to beta-cell compensation for obesity and pregnancy in animal models with morbid obesity or gestational diabetes. Such genetic factors could be potential therapeutic targets for augmenting beta-cell compensation to prevent the development of overt diabetes in at-risk individuals with gestational diabetes and type 2 diabetes. These studies are funded by grants from NICHD and NIDDK. 

Pathophysiology of insulin resistance and diabetic dyslipidemia:

A second focus of Dr. Dong's laboratory is on diabetic dyslipidemia, the most common lipid disorder in patients with obesity and type 2 diabetes. Diabetic dyslipidemia is characterized by a triad plasma lipid profile, i.e., increased triglyceride and LDL-cholesterol levels, and decreased HDL-cholesterol levels. Diabetic dyslipidemia along with hepatic insulin resistance is considered an independent risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD). Using transgenic, gene knockout and gene transfer approaches, Dr. Dong's team works to characterize the insulin-Akt-FoxO1 signaling pathway in hepatic macrophages including Kupffer cells and hepatic stellate cells. The goal of these studies is to understand how abnormal activation of Kupffer cells and hepatic stellate cells, resulting from insulin resistance, contributes to hepatic inflammation and liver fibrosis in subjects with MAFLD. These studies are expected to gain insight into the molecular events that link insulin resistance to metabolic abnormalities, providing a knowledge base for the development of small molecule drugs for better clinical management of diabetic dyslipidemia and MAFLD in patients with morbid obesity and type 2 diabetes. Dr. Dong has received funds from National Institute of Health, American Diabetes Association and Juvenile Diabetes Research Foundation.