Biomedical Research Education & Training
Faculty Member

Piston, David W., Ph.D.
Adjoint Professor of Molecular Physiology and Biophyics
Professor of Biomedical Engineering

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Phone Number: (615) 322-7030

Email Address:

Piston, David's picture
Academic history
B.A., Grinnell College, Grinnell, Iowa
M.S., University of Illinois, Urbana, Illinois
Ph.D., University of Illinois, Urbana, Illinois
Post-Doc, Cornell University, Ithaca, NY

Office Address   Mailing Address

747 Light Hall

702 Light Hall 21st Avenue South 37232-0615

Research Keywords
Glucose Metabolism Dynamics, Insulin Secretion, Non-Linear Laser Microscopy

Research Specialty
In vivo studies of stimulus-secretion coupling

Research Description
The research in our lab focuses on molecular events involved in glucose metabolism and insulin secretion in beta cells within intact functioning pancreatic islets. We have developed unique, state-of-the-art fluorescence imaging methods to assay the response at various points along the glucose transduction pathway. The quantitative microscopy is 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. As glucose is metabolized by the beta cell, there is a rise in NAD(P)H that can be monitored by its autofluorescence. Imaging of the temporal and spatial pattern of NAD(P)H has revealed that individual beta cells within the islet form a much more uniform population than was expected from studies of dissociated cells. Glucokinase dominates the rate of glucose signal transduction by beta cells, and we are investigating its allosteric regulation by protein-protein interactions with nitric oxide synthase. This interaction has not been found in vitro, but is considerable in vivo. We are also developing methods to correlate metabolic behavior to beta cell function by imaging cytoplasmic calcium activity, membrane potential, intracellular pH, and secretion of fluorescent insulin. Recently proposed models suggest that gap junctions and/or K+ channels play a role in insulin secretion from whole islets. Our new methods allow us to test these models' predictions, and thus permit determination of the important cell-cell communication mechanisms in the islet.

Chang, JC, Tomlinson, ID, Warnement, MR, Ustione, A, Carneiro, AM, Piston, DW, Blakely, RD, Rosenthal, SJ. Single molecule analysis of serotonin transporter regulation using antagonist-conjugated quantum dots reveals restricted, p38 MAPK-dependent mobilization underlying uptake activation. J Neurosci, 32(26), 8919-29, 2012

Elliott, AD, Gao, L, Ustione, A, Bedard, N, Kester, R, Piston, DW, Tkaczyk, TS. Real-time hyperspectral fluorescence imaging of pancreatic ??-cell dynamics with the image mapping spectrometer. J Cell Sci, 125(Pt 20), 4833-40, 2012

Gunawardana, SC, Piston, DW. Reversal of type 1 diabetes in mice by brown adipose tissue transplant. Diabetes, 61(3), 674-82, 2012

Head, WS, Orseth, ML, Nunemaker, CS, Satin, LS, Piston, DW, Benninger, RK. Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse. Diabetes, 61(7), 1700-7, 2012

Le Marchand, SJ, Piston, DW. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells. PLoS One, 7(10), e47084, 2012

Piston, DW. Research tools: Understand how it works. Nature, 484(7395), 440-1, 2012

Pound, LD, Sarkar, SA, Ustione, A, Dadi, PK, Shadoan, MK, Lee, CE, Walters, JA, Shiota, M, McGuinness, OP, Jacobson, DA, Piston, DW, Hutton, JC, Powell, DR, O''Brien, RM. The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One, 7(7), e40972, 2012

Schwetz, TA, Ustione, A, Piston, DW. Neuropeptide Y and Somatostatin Inhibit Insulin Secretion Through Different Mechanisms. Am J Physiol Endocrinol Metab, 2012

Ustione, A, Piston, DW. Dopamine synthesis and D3 receptor activation in pancreatic ??-cells regulates insulin secretion and intracellular [Ca(2+)] oscillations. Mol Endocrinol, 26(11), 1928-40, 2012

Benninger, RK, Head, WS, Zhang, M, Satin, LS, Piston, DW. Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet. J Physiol, 589(Pt 22), 5453-66, 2011 PMCID:3240884

Benninger, RK, Remedi, MS, Head, WS, Ustione, A, Piston, DW, Nichols, CG. Defects in beta cell CaA?+ signalling, glucose metabolism and insulin secretion in a murine model of K(ATP) channel-induced neonatal diabetes mellitus. Diabetologia, 54(5), 1087-97, 2011 PMCID:3245714

Chen, SX, Osipovich, AB, Ustione, A, Potter, LA, Hipkens, S, Gangula, R, Yuan, W, Piston, DW, Magnuson, MA. Quantification of factors influencing fluorescent protein expression using RMCE to generate an allelic series in the ROSA26 locus in mice. Dis Model Mech, 4(4), 537-47, 2011 PMCID:3124063

Higginbotham, JN, Demory Beckler, M, Gephart, JD, Franklin, JL, Bogatcheva, G, Kremers, GJ, Piston, DW, Ayers, GD, McConnell, RE, Tyska, MJ, Coffey, RJ. Amphiregulin exosomes increase cancer cell invasion. Curr Biol, 21(9), 779-86, 2011 PMCID:3240884

Kozub, J, Ivanov, B, Jayasinghe, A, Prasad, R, Shen, J, Klosner, M, Heller, D, Mendenhall, M, Piston, DW, Joos, K, Hutson, MS. Raman-shifted alexandrite laser for soft tissue ablation in the 6- to 7-??m wavelength range. Biomed Opt Express, 2(5), 1275-81, 2011

Kremers, GJ, Gilbert, SG, Cranfill, PJ, Davidson, MW, Piston, DW. Fluorescent proteins at a glance. J Cell Sci, 124(Pt 2), 157-60, 2011 PMCID:3037093

Ustione, A, Piston, DW. A simple introduction to multiphoton microscopy. J Microsc, 243(3), 221-6, 2011 PMCID:3240884

Kremers, GJ, Piston, D. Photoconversion of purified fluorescent proteins and dual-probe optical highlighting in live cells. J Vis Exp(40), 2010

Le Marchand, SJ, Piston, DW. Glucose suppression of glucagon secretion: metabolic and calcium responses from alpha-cells in intact mouse pancreatic islets. J Biol Chem, 285(19), 14389-98, 2010

Martin, MD, Kremers, GJ, Short, KW, Rocheleau, JV, Xu, L, Piston, DW, Matrisian, LM, Gorden, DL. Rapid extravasation and establishment of breast cancer micrometastases in the liver microenvironment. Mol Cancer Res, 8(10), 1319-27, 2010

Nyman, LR, Ford, E, Powers, AC, Piston, DW. Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo. Am J Physiol Endocrinol Metab, 298(4), E807-14, 2010

Palczewska, G, Maeda, T, Imanishi, Y, Sun, W, Chen, Y, Williams, DR, Piston, DW, Maeda, A, Palczewski, K. Noninvasive multiphoton fluorescence microscopy resolves retinol and retinal condensation products in mouse eyes. Nat Med, 16(12), 1444-9, 2010

Uddin, MJ, Crews, BC, Blobaum, AL, Kingsley, PJ, Gorden, DL, McIntyre, JO, Matrisian, LM, Subbaramaiah, K, Dannenberg, AJ, Piston, DW, Marnett, LJ. Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents. Cancer Res, 70(9), 3618-27, 2010

Zhao, A, Ohara-Imaizumi, M, Brissova, M, Benninger, RK, Xu, Y, Hao, Y, Abramowitz, J, Boulay, G, Powers, AC, Piston, D, Jiang, M, Nagamatsu, S, Birnbaumer, L, Gu, G. GI?o represses insulin secretion by reducing vesicular docking in pancreatic beta-cells. Diabetes, 59(10), 2522-9, 2010

Easley, CJ, Benninger, RK, Shaver, JH, Steven Head, W, Piston, DW. Rapid and inexpensive fabrication of polymeric microfluidic devices via toner transfer masking. Lab Chip, 9(8), 1119-27, 2009

Easley, CJ, Rocheleau, JV, Head, WS, Piston, DW. Quantitative measurement of zinc secretion from pancreatic islets with high temporal resolution using droplet-based microfluidics. Anal Chem, 81(21), 9086-95, 2009

Gunawardana, SC, Benninger, RK, Piston, DW. Subcutaneous transplantation of embryonic pancreas for correction of type 1 diabetes. Am J Physiol Endocrinol Metab, 296(2), E323-32, 2009

Kremers, GJ, Hazelwood, KL, Murphy, CS, Davidson, MW, Piston, DW. Photoconversion in orange and red fluorescent proteins. Nat Methods, 6(5), 355-8, 2009 PMCID:2675661

Pound, LD, Sarkar, SA, Benninger, RK, Wang, Y, Suwanichkul, A, Shadoan, MK, Printz, RL, Oeser, JK, Lee, CE, Piston, DW, McGuinness, OP, Hutton, JC, Powell, DR, O''Brien, RM. Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem J, 421(3), 371-6, 2009

Rizzo, MA, Davidson, MW, Piston, DW. Fluorescent protein tracking and detection: fluorescent protein structure and color variants. Cold Spring Harb Protoc, 2009(12), pdb.top63, 2009

de Jonge, N, Peckys, DB, Kremers, GJ, Piston, DW. Electron microscopy of whole cells in liquid with nanometer resolution. Proc Natl Acad Sci U S A, 106(7), 2159-64, 2009 PMCID:2650183

Benninger, RK, Zhang, M, Head, WS, Satin, LS, Piston, DW. Gap junction coupling and calcium waves in the pancreatic islet. Biophys J, 95(11), 5048-61, 2008

Gunawardana, SC, Head, WS, Piston, DW. Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes. Am J Physiol Endocrinol Metab, 294(6), E1097-108, 2008

Mao, S, Benninger, RK, Yan, Y, Petchprayoon, C, Jackson, D, Easley, CJ, Piston, DW, Marriott, G. Optical lock-in detection of FRET using synthetic and genetically encoded optical switches. Biophys J, 94(11), 4515-24, 2008 PMCID:2480664

Nyman, LR, Wells, KS, Head, WS, McCaughey, M, Ford, E, Brissova, M, Piston, DW, Powers, AC. Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest, 118(11), 3790-7, 2008 PMCID:2564611

Zavalin, A, Hachey, DL, Sundaramoorthy, M, Banerjee, S, Morgan, S, Feldman, L, Tolk, N, Piston, DW. Kinetics of a collagen-like polypeptide fragmentation after mid-IR free-electron laser ablation. Biophys J, 95(3), 1371-81, 2008 PMCID:2479591

Hao, M, Head, WS, Gunawardana, SC, Hasty, AH, Piston, DW. Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic {beta}-cell dysfunction. Diabetes, 56, 2328-2338, 2007

Piston, DW, Kremers, GJ. Fluorescent protein FRET: the good, the bad and the ugly. Trends Biochem Sci, 32(9), 407-14, 2007

Gunawardana, SC, Rocheleau, JV, Head, WS, Piston, DW. Mechanisms of time-dependent potentiation of insulin release: involvement of nitric oxide synthase. Diabetes, 55(4), 1029-33, 2006

Rizzo, MA, Springer, G, Segawa, K, Zipfel, WR, Piston, DW. Optimization of pairings and detection conditions for measurement of FRET between cyan and yellow fluorescent proteins. Microsc Microanal, 12(3), 238-54, 2006

Rocheleau, JV, Remedi, MS, Granada, B, Head, WS, Koster, JC, Nichols, CG, Piston, DW. Critical Role of Gap Junction Coupled K(ATP)Channel Activity for Regulated Insulin Secretion. PLoS Biol, 4(2), e26, 2006 PMCID:1334237

Hao, M, Li, X, Rizzo, MA, Rocheleau, JV, Dawant, BM, Piston, DW. Regulation of two insulin granule populations within the reserve pool by distinct calcium sources. J Cell Sci, 118(Pt 24), 5873-84, 2005

Rizzo, MA, Piston, DW. High-contrast imaging of fluorescent protein FRET by fluorescence polarization microscopy. Biophys J, 88(2), L14-6, 2005 PMCID:1305173

Rizzo, Mark A, Springer, Gerald H, Granada, Butch, Piston, David W. An improved cyan fluorescent protein variant useful for FRET. Nat Biotechnol, 22(4), 445-9, 2004

Rocheleau, Jonathan V, Head, W Steven, Piston, David W. Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response. J Biol Chem, 279(30), 31780-7, 2004

Rocheleau, Jonathan V, Walker, Glenn M, Head, W Steven, McGuinness, Owen P, Piston, David W. Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets. Proc Natl Acad Sci U S A, 101(35), 12899-903, 2004 PMCID:516492

Cricenti, A, Generosi, R, Luce, M, Perfetti, P, Margaritondo, G, Talley, D, Sanghera, JS, Aggarwal, ID, Tolk, NH, Congiu-Castellano, A, Rizzo, MA, Piston, DW. Chemically resolved imaging of biological cells and thin films by infrared scanning near-field optical microscopy. Biophys J, 85(4), 2705-10, 2003 PMCID:1303494

Rizzo, Mark A, Piston, David W. Regulation of beta cell glucokinase by S-nitrosylation and association with nitric oxide synthase. J Cell Biol, 161, 243-8, 2003 PMCID:2172922

Rocheleau, Jonathan V, Edidin, Michael, Piston, David W. Intrasequence GFP in Class I MHC Molecules, a Rigid Probe for Fluorescence Anisotropy Measurements of the Membrane Environment. Biophys J, 84, 4078-86, 2003 PMCID:1302987

Zhang, Qinghong, Piston, David W, Goodman, Richard H. Regulation of corepressor function by nuclear NADH. Science, 295(5561), 1895-7, 2002

Patterson, G H, Knobel, S M, Arkhammar, P, Thastrup, O, Piston, D W. Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells. Proc Natl Acad Sci U S A, 97(10), 5203-7, 2000 PMCID:25806

Xu, Y, Piston, D W, Johnson, C H. A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc Natl Acad Sci U S A, 96(1), 151-6, 1999 PMCID:15108

Patterson, G H, Knobel, S M, Sharif, W D, Kain, S R, Piston, D W. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys J, 73(5), 2782-90, 1997 PMCID:1181180

Bennett, B D, Jetton, T L, Ying, G, Magnuson, M A, Piston, D W. Quantitative subcellular imaging of glucose metabolism within intact pancreatic islets. J Biol Chem, 271(7), 3647-51, 1996

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