Vanderbilt University School of Medicine

Piston, David W. , Ph.D.
Director Biophotonics Institute
Professor of Molecular Physiology and Biophysics
Professor of Physics
Louise B. McGavock Chair
Professor of Chemical and Biomolecular Engineering

Lab Url:

Phone Number: (615) 322-7030


Piston, David's picture

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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