David W. Piston, Ph.D.

Edward Mallinckrodt, Jr. Professor and Head
Cell Biology and Physiology

Molecular Cell Biology Program
Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-9121

  • 8228

  • piston@wustl.edu

  • Diabetes, Biophysics, Systems Biology, Computational Biology, Hyperspectral Imaging, Glucagon

  • Studies of the Molecular Pathways of Islet Hormone Secretion

Research Abstract:

The convergence of newly developed instrumentation and optical probes allows us to examine quantitatively dynamic processes within ever more complicated biological systems. These new tools are revolutionizing almost all fields of biomedical research, and we continue to optimize such methods and expand the scope of their applicability. In our lab, research questions are focused on a model multicellular system, the islet of Langerhans, which is the functional unit responsible for glucose-stimulated insulin secretion and glucose inhibition of glucagon secretion. The islet contains glucagon secreting Alpha-cells, insulin-secreting Beta-cells, and somatostatin-secreting Delta-cells, among others. The long-term goal of our work is to understand at a quantitative molecular level the subcellular, cellular, and multicellular mechanisms of islet function, and its role in the regulation of blood glucose under normal and pathological conditions. Rotation projects are available in all the lab’s research areas. The therapeutic success of insulin has led most islet research to focus on Beta-cells, although recent findings have strengthened our understanding of glucagon’s critical role in glucose homeostasis and the pathology of diabetes. Interactions with other islet cell types are thought to be involved in glucose-inhibition of glucagon secretion, since this inhibition is lost in vivo during Type 1 and advanced Type 2 diabetes, and in vitro when Beta-cells are isolated from the islet. While many compounds have been shown to inhibit glucagon secretion from islets, no consensus model has been reached. The secretory product of Delta-cells, somatostatin, is a promising molecular mediator of this interaction, but somatostatin alone does not inhibit glucagon secretion from isolated Alpha-cells. This suggests that other cell-cell interactions within the islet are required to combine with somatostatin for proper function. Using quantitative imaging methods and novel microfluidic devices, the dynamics of these molecular mechanisms can be followed in living cells within intact islets. These investigations utilize several available transgenic and tissue-specific knock-out mouse models with demonstrated phenotypes, as well as traditional biochemical and molecular biological approaches.

Selected Publications:

Le Marchand, S.J., D.W. Piston. 2010. Metabolism and Calcium Dynamics in Glucose-Mediated Suppression of Glucagon Secretion from Alpha-Cells in Intact Pancreatic Islets. J. Biol. Chem. 285:14389-14398. PMCID: PMC2863245

Gunawardana, S.C., D.W. Piston. 2012. Reversal of Type 1 Diabetes by Brown Adipose Tissue Transplant. Diabetes. 61:674-682. PMCID: PMC3282804

Ustione, A., D.W. Piston. 2012. Dopaminergic Regulatory Feedback in Mouse Pancreatic Beta-Cells. Mol. Endocrin. 26:1928-1940. PMCID: PMC3487623

Benninger, R.K.P., T. Hutchens, W.S. Head, M. Zhang, S.J. Le Marchand, L.S. Satin, D.W. Piston. 2014. Intrinsic islet heterogeneity and coupling determine spatiotemporal calcium wave dynamics: verification of a mathematical model of the islet. Biophys. J. 107:2723-2733. PMCID: PMC425517

Elliott, A.D., A. Ustione, D.W. Piston. 2015. Somatostatin and Insulin Mediate Glucose-Inhibited Glucagon Secretion in the Pancreatic α-Cell by Lowering cAMP. Am. J. Physiol. Endocrinal. Metab. 308:E130-143. PMCID: PMC4297778

Gunawardana, S.C., D.W. Piston. 2015. Insulin-Independent Reversal of Type 1 Diabetes in Non-Obese Diabetic Mice With Brown Adipose Tissue Transplant. Am. J. Physiol. Endocrinal. Metab. 308:E1043-1055. PMCID: PMC4469812

Hutchens, T., D.W. Piston. 2015. EphA4 Receptor Forward Signaling Inhibits Glucagon Secretion in α-cells. Diabetes. 64:3839-3851. PMCID: PMC4613968

Cranfill, P.J., M.A. Baird, J. Allen, Z. Lavagnino, H.M. de Gruiter, G.-J. Kremers, M.W. Davidson, A. Ustione, D.W. Piston. 2016. Quantitative Assessment of Fluorescent Proteins. Nat. Methods. 13:557-562. PMCID: PMC4927352

Lavagnino, Z., J. Dwight, A. Ustione, T.-U. Nguyen, T.S. Tkaczyk, D.W. Piston. 2016. Snapshot hyperspectral light-sheet imaging of signal transduction dynamics in intact live pancreatic islets. Biophys. J. 111:409–417. PMCID: PMC4968423

Caldwell, B., A. Ustione, D.W. Piston. 2016. Dopamine Receptor Signaling in Insulin-Secreting MIN6 β Cells Revealed by Fluorescence Fluctuation Spectroscopy. Biophys. J. 111:609-618. PMCID: PMC4982926

Reissaus, C.A., D.W. Piston. 2017. Reestablishment of Glucose Inhibition of Glucagon Secretion in Small Pseudo-Islets. Diabetes. 66:960-969. PMCID: PMC5360306

Last Updated: 5/1/2017 11:51:48 AM

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