Anatomy, Physiology & Genetics (APG)
Uniformed Services University of the Health Sciences
4301 Jones Bridge Road
Bethesda, Maryland 20814
David Mears, Ph.D.
- Johns Hopkins University
Insulin secretion from pancreatic b-cells is tightly regulated by plasma glucose levels as well as circulating hormones and locally released neurotransmitters. Defects in the responsiveness of the b-cell to these signals lead to the development of type II diabetes mellitus. The goal of this laboratory is to elucidate the cellular and molecular mechanisms involved in physiological regulation of insulin secretion, and how these pathways are involved in the pathogenesis of diabetes. Since previous studies have shown that changes in b-cell membrane potential and intracellular Ca2+ are crucial steps in regulated insulin secretion, our particular focus is on the modulation of b-cell electrical activity and intracellular Ca2+ levels by nutrient and neurohormonal signals.
Specific ongoing projects in the laboratory include
- Investigation of the signaling pathways involved in stimulation of insulin secretion by the neurotransmitter, acetylcholine, using molecular methods to identify acetylcholine receptor subtypes in b-cells and knock-out mice to determine the functional roles of these receptors
- Studies of the roles of intracellular Ca2+ stores and store-operated ionic currents in the regulation of insulin secretion, using fluorescent intracellular Ca2+ indicators and direct ionic current measurements from rodent and human b-cells
- Studies of b-cell function and dysfunction in psammomys obesus, an animal model of dietary induced obesity and diabetes.