Farhi, Leon S.
Associate Professor of Research, Medicine: Endocrinology and Metabolism
Understanding the mechanisms that regulate glucagon secretion, glucose homeostasis, and growth hormone release. Mathematical modeling of hormone networks. Diabetes, hypoglycemia, artificial pancreas technology.
My research is in the field of systems endocrinology and focuses on the endocrine mechanisms and relationships between the different cell types in the islets of Langerhans that direct the time-varying secretion patterns of the pancreatic hormones. We are interested in the mechanisms of glucagon release from the ?-cells in response to hypoglycemia, study how these mechanisms are altered in diabetes, and seek to develop strategies for their repair. Through series of interdisciplinary experimental and clinical in vivo work and mathematical modeling in silico studies, we have shown that the abnormalities in the glucagon defenses against hypoglycemia in diabetes are mediated in part by miscommunication between the different cell types in the pancreatic islets and are essentially of "network origin". The lack of ?-cell signaling is the primary deficiency that contributes to two separate network defects: (i) absence of a "switch-off" trigger to the ?-cells and (ii) increased intraislet basal glucagon. We have experimental evidence suggesting that both defects can be potentially repaired by therapeutic strategies based on the use of ?-cell inhibiting drugs.
To further test the hypothesis that ?-cell inhibitors can be used to manipulate the pancreatic network to enhance the glucagon response to hypoglycemia and start translation of our findings into the clinic our lab collaborates with the UVA Center for Diabetes Technology. Taking advantage of the Center's cutting-edge artificial pancreas technologies we work on the development of strategies for dual-hormone automated glucose control in patients with type 1 diabetes that use both insulin and ?-cell inhibiting drugs. The addition of an ?-cell inhibitor as a second control mechanism is expected to allow us to manipulate the pancreatic endocrine network to achieve better glycemic control with reduced hypoglycemia risk.