Matthew Whim, Ph.D.

Control of glucose homeostasis by the autonomic nervous system.

We are interested in the neuronal mechanisms that regulate the levels of blood glucose. Ensuring that enough energy-rich molecules, including glucose and fatty acids, are present in the plasma is essential for life. If the levels drop too low, hypoglycemia and coma can ensue. If the levels are too high this increases the risk of obesity and diabetes. It is clear that the nervous system plays a central role in this homeostatic process. Our particular interest is in determining how the autonomic nervous system controls the response to hypoglycemia. When the level of blood glucose falls below a threshold value the neuroendocrine chromaffin cells in the adrenal medulla become progressively activated and as a result epinephrine secretion is increased. This hormone acts on the liver to increase glucose production and on the pancreas to inhibit insulin secretion: both actions help to restore euglycemia.

My lab is investigating the signaling mechanisms that underlie this release of epinephrine. In this work we use a variety of experimental approaches including slice electrophysiology, optogenetics and in vivo measurements of circulating hormones and metabolites. We would like to understand how the adrenal response to hypoglycemia is initiated, how it is regulated and why it sometimes fails. The importance of the adrenal contribution to metabolic regulation is exemplified by the clinical problems experienced by type I and II diabetics in whom the response is markedly deficient.