Modulation of Three Types of Potassium Selective Channels by NAD and Other Pyridine Nucleotides in Human Pancreatic β-Cells

NAD and K+ Channels in Human β-Cells
  • E. A. Harding
  • C. Kane
  • R. F. L. James
  • N. J. M. London
  • M. J. Dunne
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 426)


ATP-regulated potassium (K+ATP) channels play a major role in control of the cell membrane potential in pancreatic β-cells, and therefore, nutrient-induced insulin secretion (for recent reviews see 1–4). It has been well documented that glucose-induced closure of these channels is involved in the initial depolarisation of the membrane(5), and widely accepted that this may occur through an increase in the intracellular ATP:ADP ratio which is responsible for coupling metabolic events to ionic events at the plasma membrane(1,2,4). However, other intracellular modulators of K+ATP channels could also be involved in the regulation of the complex cycles of electrical activity exhibited by the cells in response to glucose stimulation. Changes in the redox potential of the nicotine adenine dinucleotides NAD(P)/NAD(P)H have for many years been thought to be important intracellular signals that could mediate the effects of nutrient secretagogues on insulin secretion(6–9). In more recent studies it has been demonstrated using rodent β-cells stimulated with glucose that increases in the concentration of NAD(P)H occur prior to an increase in [Ca2+]i(10, 11), and also that all four of the pyridine nucleotides will modulate the gating of ATP-sensitive K+ channels in the RINm5F insulin-secreting cell line(12). Using patch clamp techniques we have now examined the effects of NAD and other pyridine nucleotides on the gating of three types of K+ channel in human pancreatic β-cells; the K+ATP channel, the Ca2+ and voltage gated channel, and a novel NAD-activated K+ channel.


Human Islet Pyridine Nucleotide Channel Inactivation RINm5F Cell United Kingdom Introduction 
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  1. 1.
    Ashcroft, F.M., and Rorsman, P., 1989, Electrophysiology of the pancreatic β-cell, Prog. Biophys. Mol. Biol. 54: 87–143.PubMedCrossRefGoogle Scholar
  2. 2.
    Dunne, M.J., and Petersen, O.H., 1991, Potassium selective ion channels in insulin secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling, Biochem. Biophys. Acta 1071: 67–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Misler, S., Barnett, D.W., Gillis, K.D., and Pressel, D.M., 1992, Electrophysiology of stimulus-secretion coupling in human beta-cells Diabetes 41: 1221–1228.PubMedCrossRefGoogle Scholar
  4. 4.
    Dunne, M.J., Harding, E.A., Jaggar, J.H., and Squires, P.E., 1994, Ion channels and the molecular control of insulin secretion, Biochem. Soc. Trans. 22: 6–12.PubMedGoogle Scholar
  5. 5.
    Ashcroft, F.M., Harrison, D.E., and Ashcroft, S.J.H., 1984, Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells, Nature 312: 446–448.PubMedCrossRefGoogle Scholar
  6. 6.
    Panten, U., Christians, J., Kriegstein, E. von, Poser, W., and Hasselblatt, A., 1973, Effects of carbohydrates upon fluorescence of reduced pyridine nucleotides from perifused isolated pancreatic islets, Diabetologia 9: 477–482.PubMedCrossRefGoogle Scholar
  7. 7.
    Ashcroft, S.J.H., and Christie, M.R., 1979, Effects of glucose on the cytosolic ratio of reduced/oxidised nicotinamine-adenine di-nucleotide phosphate in rat islets of Langerhans, Biochem J 184: 697–700.PubMedGoogle Scholar
  8. 8.
    Malaisse, W.J., Hutton, J.C., Kawazu, S., Herchuelz, A., Valverde, I., and Sener, A. 1979, The stimulus secretion coupling of glucose-induced insulin release: XXXV. The links between metabolic and cationic events, Diabetologia 16: 331–341.PubMedCrossRefGoogle Scholar
  9. 9.
    Matschinsky, F.M., Gosh, A.K., Meglasson, M.D., Prentki, M., June, V., and Allman, D. von, 1986, Metabolic concomitants in pure, pancreatic beta cells during glucose-stimulated insulin secretion, J. Biol. Chem. 261: 14057–14061.PubMedGoogle Scholar
  10. 10.
    Pralong, W.F., Bartley, C., and Wollheim, C.B., 1990, Single islet beta-cell stimulation by nutrients: relationship between pyridine nucleotides, cytosolic calcium and secretion, EMBO J. 9: 53–60.PubMedGoogle Scholar
  11. 11.
    Gilon, P., and Henquin, J.C., 1992, Influence of membrane potential changes on cytoplasmic calcium concentration in an electrically excitable cell, the insulin-secreting pancreatic β-cell, J. Biol. Chem. 267: 20713–20720.PubMedGoogle Scholar
  12. 12.
    Dunne, M.J., Findlay, I., and Petersen, O.H., 1988, The effects of pyridine nucleotides on the gating of ATP-sensitive K+ channels in insulin-secreting cells, J. Membr. Biol. 102: 205–216.PubMedCrossRefGoogle Scholar
  13. 13.
    London, N.J.M., James, R.F.L., and Bell, P.R.F., 1992, Islet purification. In: Pancreatic islet cell transplantation. Ed C. Ricordi, pp 113–123. RG Landes Press, UK.Google Scholar
  14. 14.
    Squires, P.E., James, R.F.L., London, N.J.M., and Dunne, M.J. 1994, ATP-induced intracellular Ca2+ signals in isolated human insulin-secreting cells, Pflugers Arch., 421: 181–183.CrossRefGoogle Scholar
  15. 15.
    Findlay, I., and Dunne, M.J., 1986 ATP maintains ATP-inhibited K+ channels in an operational state, Pflugers Arch. 407: 238–240.PubMedCrossRefGoogle Scholar
  16. 16.
    Misler, S., Falke, L.C., Gillis, K.D., and McDaniel, M.L., 1986, A metabolite regulated potassium channel in rat pancreatic β-cells, Proc Natl Acad Sci USA 83: 7119–7123.PubMedCrossRefGoogle Scholar
  17. 17.
    Ashcroft, F.M., Kakei, M., Gibson, J.S., Gray, D.W., Sutton, R., 1989, The ATP-and tolbutamide sensitivity of the ATP-sensitive potassium channel from human pancreatic beta cells, Diabetologia 32: 591–598.PubMedCrossRefGoogle Scholar
  18. 18.
    Misler, S., Gee, W.M., Gillis, K.D., Scharp, D.W., Falke, L.C., 1989, Metabolite-regulated ATP-sensitive potassium channel in human pancreatic islet cells, Diabetes 38: 422–427.PubMedCrossRefGoogle Scholar
  19. 19.
    Pressel, D.M., and Misler, S., 1990, Sodium channels contribute to action potential generation in canine and human pancreatic islet B cells, J. Membr. Biol. 116: 273–280.PubMedCrossRefGoogle Scholar
  20. 20.
    Kelly, R.P., Sutton, R., and Ashcroft, F.M., 1991, Voltage-activated calcium and potassium currents in human pancreatic beta-cells, J. Physiol. 443: 175–192.PubMedGoogle Scholar
  21. 21.
    Misler, S., Barnett, D.W., and Falke, L.C., 1992, Effects of metabolic inhibition by sodium azide on stimulus-secretion coupling in β-cells of human islets of Langerhans, Pflugers Arch. 421: 289–291.PubMedCrossRefGoogle Scholar
  22. 22.
    Misler, S., Barnett, D.W., Pressel, D.M., Gillis, K.D., Scharp, D.W., Falke, L.C., 1992, Stimulus-secretion coupling in beta-cells of transplantable human islets of Langerhans: Evidence for a critical role for calcium entry, Diabetes 41: 662–670.PubMedCrossRefGoogle Scholar
  23. 23.
    Williams, B.A., Smith, P.A., Leow, K., Shimizu, S., Gray, D.W., and Ashcroft, F.M. 1993, Two types of potassium channel regulated by ATP in pancreatic β-cells isolated from a type-2 diabetic human, Pflugers Arch. 423: 265–273.PubMedCrossRefGoogle Scholar
  24. 24.
    Sturgess, N.C., Hales, C.N., and Ashford, M.L.J., 1986, Inhibition of a calcium-activated non-selective cation channel in a rat insulinoma cell line, by adenine derivatives, FEBS Letts 208: 397–400.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • E. A. Harding
    • 1
  • C. Kane
    • 1
  • R. F. L. James
    • 2
  • N. J. M. London
    • 2
  • M. J. Dunne
    • 1
  1. 1.Department of Biomedical ScienceThe University of SheffieldWestern Bank SheffieldUK
  2. 2.School of MedicineThe University of Leicester Department of SurgeryLeicesterUK

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