The main research focus of the Piston lab is the understanding of glucose-regulated hormone (insulin, glucagon, and somatostatin) secretion from islets of Langerhans in the pancreas. To perform measurements on the constituent cell types in situ and in vivo, we have developed unique, state-of-the-art fluorescence imaging methods to assay the response at various points along the glucose transduction pathway. Quantitative microscopy experiments are combined with standard biochemical and molecular biological techniques to obtain unique information that bridges the gap between the known details of the glucose transduction pathway in individual beta cells and the overall glucose response of a whole islet. Recently proposed mathematical models predict specific behaviors of the islet arising from cell-cell coupling by gap junctions and paracrine communication. These include hormonal communication mechanisms between cells within the islet, as well as from gut incretins and other extra-pancreatic sources. Over the last 20 years, we have developed both instrumentation and probe technology for the required quantitative measurements, and this technology is all broadly applicable to cell biology, tissue, physiology, and whole organism imaging experiments. Many properties of intact islets match those seen in vivo, and we are focusing on methods that allow us to assay living islet functions quantitatively, and these studies are proving critical to advancing our understanding of the regulation of glucagon secretion from α-cells. We have also developed approaches to collect and analyze appropriate in vivo data to correlate with the isolated islet results, for example data on gut incretins.
