Long-term effects of unhealthy prenatal enviornmental factors on off spring pancreatic beta cells - It is well known that various unhealthy prenatal environmental factors such as maternal diabetes, obesity, malnutrition and intermittent hypoxia increase offspring risk for obesity, glucose intolerance, and type 2 diabetes mellitus in adulthood. However, the underlying mechanisms to alter pancreatic beta cell development and programming and lead to beta cell vulnerability in later life are not known, and little information is available to reveal the mechanisms. The goal of this project is to understand these mechanisms in the offspring affected by various unhealthy prenatal factors.

Metabolic regulation in pancreatic beta cells - Type 2 diabetes mellitus is characterized by insulin resistance and beta cell failure. Once insulin resistance occurs, pancreatic beta cell must secrete more insulin to maintain normal glucose levels. Increased insulin secretion requires beta cell adaptation, a process that includes increased beta cell mass and enhanced insulin secretion. In type 2 diabetes mellitus, there is a failure of beta cell adaptation. Glucose metabolism in beta cell is well known to regulate beta cell insulin secretion and other function, however, metabolic regulation in beta cell is not well known during the development of type 2 diabetes. The goal of this project is to understand glucose metabolic changes in pancreatic beta cells in obese and type 2 diabetic animal models.

Pancreatic exocrine insufficiency in diabetic animal models - Pancreatic exocrine acinar cells make and secrete many kinds of enzymes for digesting starch, fat and protein. It is recognized that diabetic patients may have a deficit of the exocrine function manifested by loss of appetite, delayed gastric emptying, malnutrition and loss of body weight. The underlying mechanisms to cause exocrine insufficiency are not well known. We hypothesize that hyperglycemia increases free radical oxygen species in pancreas that damage acinar cells. This hypothesis will be tested in diabetic animal models. The final goal of this project is to uncover the mechanisms and develop methods to prevent and treat exocrine insufficiency in diabetic patients.