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.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Quantitative assessment of fluorescent proteins. Cranfill PJ, Sell BR, Baird MA, Allen JR, Lavagnino Z, de Gruiter HM, Kremers GJ, Davidson MW, Ustione A, Piston DW (2016) Nat Methods 13(7): 557-62
    › Primary publication · 27240257 (PubMed) · PMC4927352 (PubMed Central)
  2. Electron Microscopy of Living Cells During in Situ Fluorescence Microscopy. Liv N, van Oosten Slingeland DS, Baudoin JP, Kruit P, Piston DW, Hoogenboom JP (2016) ACS Nano 10(1): 265-73
    › Primary publication · 26580231 (PubMed) · PMC4729641 (PubMed Central)
  3. EphA4 Receptor Forward Signaling Inhibits Glucagon Secretion From α-Cells. Hutchens T, Piston DW (2015) Diabetes 64(11): 3839-51
    › Primary publication · 26251403 (PubMed) · PMC4613968 (PubMed Central)
  4. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Gunawardana SC, Piston DW (2015) Am J Physiol Endocrinol Metab 308(12): E1043-55
    › Primary publication · 25898954 (PubMed) · PMC4469812 (PubMed Central)
  5. Host and tumor derived MMP13 regulate extravasation and establishment of colorectal metastases in the liver. Mendonsa AM, VanSaun MN, Ustione A, Piston DW, Fingleton BM, Gorden DL (2015) Mol Cancer : 49
    › Primary publication · 25880591 (PubMed) · PMC4351934 (PubMed Central)
  6. Biophysical Journal special issue: focus on quantitative cell biology. Piston DW (2014) Biophys J 107(11): E01
    › Primary publication · 25468353 (PubMed) · PMC4255198 (PubMed Central)
  7. Intrinsic islet heterogeneity and gap junction coupling determine spatiotemporal Ca²⁺ wave dynamics. Benninger RK, Hutchens T, Head WS, McCaughey MJ, Zhang M, Le Marchand SJ, Satin LS, Piston DW (2014) Biophys J 107(11): 2723-33
    › Primary publication · 25468351 (PubMed) · PMC4255172 (PubMed Central)
  8. Fluorescent probes of the apoptolidins and their utility in cellular localization studies. DeGuire SM, Earl DC, Du Y, Crews BA, Jacobs AT, Ustione A, Daniel C, Chong KM, Marnett LJ, Piston DW, Bachmann BO, Sulikowski GA (2015) Angew Chem Int Ed Engl 54(3): 961-4
    › Primary publication · 25430909 (PubMed) · PMC4293314 (PubMed Central)
  9. Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP. Elliott AD, Ustione A, Piston DW (2015) Am J Physiol Endocrinol Metab 308(2): E130-43
    › Primary publication · 25406263 (PubMed) · PMC4297778 (PubMed Central)
  10. Differential stimulation of insulin secretion by GLP-1 and Kisspeptin-10. Schwetz TA, Reissaus CA, Piston DW (2014) PLoS One 9(11): e113020
    › Primary publication · 25401335 (PubMed) · PMC4234631 (PubMed Central)
  11. NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression. Grabowska MM, Elliott AD, DeGraff DJ, Anderson PD, Anumanthan G, Yamashita H, Sun Q, Friedman DB, Hachey DL, Yu X, Sheehan JH, Ahn JM, Raj GV, Piston DW, Gronostajski RM, Matusik RJ (2014) Mol Endocrinol 28(6): 949-64
    › Primary publication · 24801505 (PubMed) · PMC4042066 (PubMed Central)
  12. Cellular communication and heterogeneity in pancreatic islet insulin secretion dynamics. Benninger RK, Piston DW (2014) Trends Endocrinol Metab 25(8): 399-406
    › Primary publication · 24679927 (PubMed) · PMC4112137 (PubMed Central)
  13. Inhibition of pancreatic β-cell Ca2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance. Dadi PK, Vierra NC, Ustione A, Piston DW, Colbran RJ, Jacobson DA (2014) J Biol Chem 289(18): 12435-45
    › Primary publication · 24627477 (PubMed) · PMC4007438 (PubMed Central)
  14. The MafA transcription factor becomes essential to islet β-cells soon after birth. Hang Y, Yamamoto T, Benninger RK, Brissova M, Guo M, Bush W, Piston DW, Powers AC, Magnuson M, Thurmond DC, Stein R (2014) Diabetes 63(6): 1994-2005
    › Primary publication · 24520122 (PubMed) · PMC4030115 (PubMed Central)
  15. Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer. Schietinger A, Arina A, Liu RB, Wells S, Huang J, Engels B, Bindokas V, Bartkowiak T, Lee D, Herrmann A, Piston DW, Pittet MJ, Lin PC, Zal T, Schreiber H (2013) Oncoimmunology 2(11): e26677
    › Primary publication · 24482750 (PubMed) · PMC3895414 (PubMed Central)
  16. A microfluidic-enabled mechanical microcompressor for the immobilization of live single- and multi-cellular specimens. Yan Y, Jiang L, Aufderheide KJ, Wright GA, Terekhov A, Costa L, Qin K, McCleery WT, Fellenstein JJ, Ustione A, Robertson JB, Johnson CH, Piston DW, Hutson MS, Wikswo JP, Hofmeister W, Janetopoulos C (2014) Microsc Microanal 20(1): 141-51
    › Primary publication · 24444078 (PubMed) · PMC4026272 (PubMed Central)
  17. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM (2014) Cell 156(1-2): 304-16
    › Primary publication · 24439384 (PubMed) · PMC3922400 (PubMed Central)
  18. Connexin 36 mediates blood cell flow in mouse pancreatic islets. Short KW, Head WS, Piston DW (2014) Am J Physiol Endocrinol Metab 306(3): E324-31
    › Primary publication · 24326425 (PubMed) · PMC3920012 (PubMed Central)
  19. A motion correction framework for time series sequences in microscopy images. Kumar AN, Short KW, Piston DW (2013) Microsc Microanal 19(2): 433-50
    › Primary publication · 23410911 (PubMed) · PMC4135398 (PubMed Central)
  20. Chapter 4: Combining microfluidics and quantitative fluorescence microscopy to examine pancreatic islet molecular physiology. Rocheleau JV, Piston DW (2008) Methods Cell Biol : 71-92
    › Primary publication · 19118673 (PubMed)
  21. Gap junction coupling and calcium waves in the pancreatic islet. Benninger RK, Zhang M, Head WS, Satin LS, Piston DW (2008) Biophys J 95(11): 5048-61
    › Primary publication · 18805925 (PubMed) · PMC2586567 (PubMed Central)
  22. Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Martin MD, Fingleton B, Lynch CC, Wells S, McIntyre JO, Piston DW, Matrisian LM (2008) Clin Exp Metastasis 25(8): 877-85
    › Primary publication · 18787962 (PubMed) · PMC2588650 (PubMed Central)
  23. Regulation of two insulin granule populations within the reserve pool by distinct calcium sources. Hao M, Li X, Rizzo MA, Rocheleau JV, Dawant BM, Piston DW (2005) J Cell Sci 118(Pt 24): 5873-84
    › Primary publication · 16317050 (PubMed)
  24. Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response. Rocheleau JV, Head WS, Piston DW (2004) J Biol Chem 279(30): 31780-7
    › Primary publication · 15148320 (PubMed)
  25. Regulation of beta cell glucokinase by S-nitrosylation and association with nitric oxide synthase. Rizzo MA, Piston DW (2003) J Cell Biol 161(2): 243-8
    › Primary publication · 12707306 (PubMed) · PMC2172922 (PubMed Central)
  26. Substrate-induced nuclear export and peripheral compartmentalization of hepatic glucokinase correlates with glycogen deposition. Jetton TL, Shiota M, Knobel SM, Piston DW, Cherrington AD, Magnuson MA (2001) Int J Exp Diabetes Res 2(3): 173-86
    › Primary publication · 12369705 (PubMed) · PMC2478546 (PubMed Central)
  27. A functional link between glucokinase binding to insulin granules and conformational alterations in response to glucose and insulin. Rizzo MA, Magnuson MA, Drain PF, Piston DW (2002) J Biol Chem 277(37): 34168-75
    › Primary publication · 12101177 (PubMed)
  28. Pancreatic islet beta-cells transiently metabolize pyruvate. Rocheleau JV, Head WS, Nicholson WE, Powers AC, Piston DW (2002) J Biol Chem 277(34): 30914-20
    › Primary publication · 12070148 (PubMed)
  29. Quantitative imaging of metabolism by two-photon excitation microscopy. Piston DW, Knobel SM (1999) Methods Enzymol : 351-68
    › Primary publication · 10506984 (PubMed)
  30. Quantitative imaging of the green fluorescent protein (GFP). Piston DW, Patterson GH, Knobel SM (1999) Methods Cell Biol : 31-48
    › Primary publication · 9891373 (PubMed)
  31. Adenovirus-mediated knockout of a conditional glucokinase gene in isolated pancreatic islets reveals an essential role for proximal metabolic coupling events in glucose-stimulated insulin secretion. Piston DW, Knobel SM, Postic C, Shelton KD, Magnuson MA (1999) J Biol Chem 274(2): 1000-4
    › Primary publication · 9873043 (PubMed)
  32. Quantitative imaging of TATA-binding protein in living yeast cells. Patterson GH, Schroeder SC, Bai Y, Weil A, Piston DW (1998) Yeast 14(9): 813-25
    › Primary publication · 9818719 (PubMed)
  33. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Patterson GH, Knobel SM, Sharif WD, Kain SR, Piston DW (1997) Biophys J 73(5): 2782-90
    › Primary publication · 9370472 (PubMed) · PMC1181180 (PubMed Central)
  34. Quantitative subcellular imaging of glucose metabolism within intact pancreatic islets. Bennett BD, Jetton TL, Ying G, Magnuson MA, Piston DW (1996) J Biol Chem 271(7): 3647-51
    › Primary publication · 8631975 (PubMed)
  35. Quantitative imaging of green fluorescent protein in cultured cells: comparison of microscopic techniques, use in fusion proteins and detection limits. Niswender KD, Blackman SM, Rohde L, Magnuson MA, Piston DW (1995) J Microsc 180(Pt 2): 109-16
    › Primary publication · 8537958 (PubMed)