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Significance of Ionic Fluxes and Changes in Membrane-potential for Stimulus-secretion Coupling in Pancreatic B-cells

Bibliographic reference Henquin, Jean-Claude ; Meissner, HP.. Significance of Ionic Fluxes and Changes in Membrane-potential for Stimulus-secretion Coupling in Pancreatic B-cells. In: Experientia, Vol. 40, no. 10, p. 1043-1052 (1984)
Permanent URL http://hdl.handle.net/2078.1/55800
  1. Asplund K., Sehlin J., Täljedal I.-B., Effects of glucose, chloromercuribenzene-p-sulphonic acid and 4-acetamido-4′-isothiocyanostilbene-2,2′- disulphonic acid on phosphate efflux from pancreatic islets, 10.1016/0304-4165(79)90206-x
  2. Atwater, I., Control mechanisms for glucose-induced changes in the membrane potential of mouse pancreatic β-cell. Cienc. Biol.5 (1980) 299–314.
  3. Atwater, I., Dawson, C.M., Ribalet, B., and Rojas, E., Potassium permeability activated by intracellular calcium ion concentration in the pancreatic β cell. J. Physiol.288 (1979) 575–588.
  4. Atwater Illani, Frankel Barbara J., Rojas Eduardo, Grodsky Gerold M., β CELL MEMBRANE POTENTIAL AND INSULIN RELEASE; ROLE OF CALCIUM AND CALCIUM: MAGNESIUM RATIO, 10.1113/expphysiol.1983.sp002715
  5. Atwater I, Goncalves A, Herchuelz A, Lebrun P, Malaisse W J, Rojas E, Scott A, Cooling dissociates glucose-induced insulin release from electrical activity and cation fluxes in rodent pancreatic islets., 10.1113/jphysiol.1984.sp015129
  6. Atwater, I., Goncalves, A.A., and Rojas, E., Electrophysiological measurement of an oscillating potassium permeability during the glucose-stimulated burst activity in mouse pancreatic β-cell. Biomed. Res.3 (1982) 645–648.
  7. Atwater, I., and Meissner, H.P., Electrogenic sodium pump in β-cells of islets of Langerhans. J. Physiol.247 (1975) 56–58P.
  8. Atwater I, Ribalet B, Rojas E, Cyclic changes in potential and resistance of the beta-cell membrane induced by glucose in islets of Langerhans from mouse., 10.1113/jphysiol.1978.sp012296
  9. Beigelman, P.M., Ribalet, B., and Atwater, I., Electrical activity of mouse pancreatic beta-cells. II. Effects of glucose and arginine. J. Physiol., Paris73 (1977) 201–217.
  10. Berggren, P.O., Bergsten, P., Gylfe, E., Larsson, R., and Hellman, B., Interactions between magnesium and calcium in β-cell-rich pancreatic islets. Am. J. Physiol.244 (1983) E541-E547.
  11. Berglund, O., Sehlin, J., and Täljedal, I.-B., Influence of the murine diabetes gene on rubidium ion efflux from perifused islets. Diabetologia19 (1980) 45–49.
  12. Boschero, A.C., Kawazu, S., Duncan, G., and Malaisse, W.J., Effect of glucose on K+ handling by pancreatic islets. FEBS Lett.83 (1977) 151–154.
  13. Boschero, A.C., and Malaisse, W.J., Stimulus-secretion coupling of glucose-induced insulin release. Regulation of86Rb+ efflux from perifused islets. Am. J. Physiol.236 (1979) E139-E146.
  14. Bukowiecki Ludwik, Trus Michael, Matschinsky Franz M., Freinkel Norbert, Alterations in pancreatic islet phosphate content during secretory stimulation with glucose, 10.1016/0304-4165(79)90461-6
  15. Carpinelli, A.R., and Malaisse, W.J., Regulation of86Rb outflow from pancreatic islets. Effect of changes in extracellular and intracellular pH. Diabète Métab.6 (1980) 193–198.
  16. Carpinelli, A.R., and Malaisse, W.J., The stimulus-secretion coupling of glucose-induced insulin release. A possible link between glucose metabolism and phosphate flush. Diabetologia19 (1980) 458–464.
  17. Cook, D.L., Isolated islets of Langerhans have slow oscillations of electrical activity. Metabolism32 (1983) 681–685.
  18. Cook, D.L., Crill, W.E., and Porte, D., Glucose and acetylcholine have different effects on the plateau pacemaker of pancreatic islet cells. Diabetes30 (1981) 558–561.
  19. Cook, D.L., and Perera, E., Islet electrical pacemaker response to alpha-adrenergic stimulation. Diabetes31 (1982) 985–990.
  20. Cook, D.L., Porte, D., and Crill, W.E., Voltage dependence of rhythmic plateau potentials of pancreatic islet cells. Am. J. Physiol.240 (1981) E290-E296.
  21. Curry, D.L., Joy, R.M., Holley, D.C., and Bennett, L.L., Magnesium modulation of glucose-induced insulin secretion by the perfused rat pancreas. Endocrinology101 (1977) 203–208.
  22. Dawson, C.M., Croghan, P.C., Atwater, I., and Rojas, E., Estimation of potassium permeability in mouse islets of Langerhans. Biomed. Res.4 (1983) 389–392.
  23. Dean, P.M., and Matthews, E.K., Electrical activity in pancreatic islet cells. Nature219 (1968) 389–390.
  24. Dean, P.M., and Matthews, E.K., Alloxan on islet cell membrane potentials. Br. J. Pharmac.34 (1968) 677.
  25. Dean P. M., Matthews E. K., Glucose-induced electrical activity in pancreatic islet cells, 10.1113/jphysiol.1970.sp009207
  26. Dean P. M., Matthews E. K., Electrical activity in pancreatic islet cells: effect of ions, 10.1113/jphysiol.1970.sp009208
  27. Dean P M, Matthews E K, Sakamoto Y, Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity., 10.1113/jphysiol.1975.sp010899
  28. Deleers, M., Lebrun, P., and Malaisse, W.J., Increase in bicarbonate influx and cellular pH in glucose-stimulated pancreatic islets. FEBS Lett.154 (1983) 97–100.
  29. Dunham, P.B., Stewart, G.W., and Ellory, J.C., Chloride-activated passive potassium transport in human erythrocytes. Proc. natl Acad. Sci. USA77 (1980) 1711–1715.
  30. Eddlestone, G.T., and Beigelman, P.M., Pancreatic β-cell electrical activity: the role of anions and the control of pH. Am. J. Physiol.244 (1983) C188-C197.
  31. Freinkel N., Phosphate Translocations during Secretory Stimulation of Pancreatic Islets, Treatment of EARLY DIABETES (1979) ISBN:9781461591122 p.71-77, 10.1007/978-1-4615-9110-8_12
  32. Freinkel, N., El Younsi, C., Bonnar, J., and Dawson, R.M.C., Rapid transient efflux of phosphate ion from pancreatic islets as an early action of insulin secretagogues. J. clin. Invest.54 (1974) 1179–1189.
  33. Gagerman, E., Idahl, L.A., Meissner, H.P., and Täljedal, I.-B., Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets. Am. J. Physiol.235 (1978) E493-E500.
  34. Gagerman E., Sehlin J., Täljedal I.-B., Effects of acetylcholine on ion fluxes and chlorotetracycline fluorescence in pancreatic islets, 10.1113/jphysiol.1980.sp013175
  35. Grodsky G. M., Bennett L. L., Cation Requirements for Insulin Secretion in the Isolated Perfused Pancreas, 10.2337/diab.15.12.910
  36. Hales C. N., Milner R. D. G., The role of sodium and potassium in insulin secretion from rabbit pancreas, 10.1113/jphysiol.1968.sp008433
  37. Hedeskov, C.J., Mechanism of glucose-induced insulin secretion. Physiol. Rev.60, (1980) 442–509.
  38. Hellman Bo, Idahl Lars-Åke, Lernmark Åke, Sehlin Janove, Täljedal Inge-Bert, The pancreatic β-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release, 10.1042/bj1380033
  39. Henquin, J.C., D-glucose inhibits potassium efflux from pancreatic islet cells. Nature271 (1978) 271–273.
  40. Henquin, J.C., Opposite effects of intracellular Ca2+ and glucose on K+ permeability of pancreatic islet cells. Nature280 (1979) 66–68.
  41. Henquin Jean-Claude, Metabolic control of the potassium permeability in pancreatic islet cells, 10.1042/bj1860541
  42. Henquin, J.C., The potassium permeability of pancreatic islet cells: mechanisms of control and influence on insulin release. Horm. Metab. Res., suppl.10 (1980) 66–73.
  43. Henquin, J.C., The effect of pH on86rubidium efflux from pancreatic islet cells. Molec. cell. Endocr.21 (1981) 119–128.
  44. Henquin Jean-Claude, Lambert Andre E., Extracellular bicarbonate ions and insulin secretion, 10.1016/0304-4165(75)90251-2
  45. Henquin, J.C., and Lambert, A.E., Bicarbonate modulation of glucose-induced biphasic insulin release by rat islets. Am. J. Physiol.231 (1976) 713–721.
  46. Henquin, J.C., and Meissner, H.P., Effects of amino acids on membrane potential and86Rb+ fluxes in pancreatic β-cells. Am. J. Physiol.240 (1981) E245-E252.
  47. Henquin J. C., Meissner H. P., The electrogenic sodium-potassium pump of mouse pancreatic B-cells, 10.1113/jphysiol.1982.sp014429
  48. Henquin, J.C., and Meissner, H.P., Opposite effects of tolbutamide and diazoxide on86Rb+ fluxes and membrane potential in pancreatic B cells. Biochem. Pharmac.31 (1982) 1407–1415.
  49. Henquin, J.C., and Meissner, H.P., Dibutyrul cyclic AMP triggers Ca2+ influx and Ca2+-dependent electrical activity in pancreatic B cells. Biochem. biophys. Res. Commun.112 (1983) 614–620.
  50. Henquin, J.C., and Meissner, H.P. The ionic, electrical, and secretory effects of endogenous cyclic adenosine monophosphate in mouse pancreatic B-cells: studies with forskolin. Endocrinology115 (1984) in press.
  51. Henquin J C, Meissner H P, Effects of theophylline and dibutyryl cyclic adenosine monophosphate on the membrane potential of mouse pancreatic beta-cells., 10.1113/jphysiol.1984.sp015265
  52. Henquin J.C., Meissner H.P., Preissler M., 9-aminoacridine- and tetraethylammonium -induced reduction of the potassium permeability in pancreatic B-cells, 10.1016/0304-4165(79)90010-2
  53. Henquin, J.C., Meissner, H.P., and Schmeer, W., Cyclic variations of glucose-induced electrical activity in pancreatic B-cells. Pflügers Arch.393 (1982) 322–327.
  54. Henquin, J.C., Schmeer, W., and Meissner, H.P., Forskolin, an activator of adenylate cyclase, increases Ca2+-dependent electrical activity induced by glucose in mouse pancreatic B cells. Endocrinology112 (1983) 2218–2220.
  55. Henquin, J.C., Tamagawa, T., Nenquin, M., and Cogneau, M., Glucose modulates Mg2+ fluxes in pancreatic islet cells. Nature301 (1983) 73–74.
  56. Henquin, J.C., Tamagawa, T., Nenquin, M., and Cogneau, M., Regulation de l'efflux de Mg dans les îlots de Langerhans de rat. J. Physiol., Paris79 (1984) 26A.
  57. Howell S. L., Taylor K W, Potassium ions and the secretion of insulin by islets of Langerhans incubatedin vitro, 10.1042/bj1080017
  58. Hutton, J.C., Sener, A., Herchuelz, A., Atwater, I., Kawazu, S., Boschero, A.C., Somers, G., Devis, G., and Malaisse, W.J., Similarities in the stimulus-secretion coupling mechanisms of glucose and 2-keto acid-induced insulin release. Endocrinology106 (1980) 203–219.
  59. Ikeuchi, M., Fujimoto, W.Y., and Cook, D.L., Rat islet cells have glucose-dependent periodic electrical activity. Horm. Metab. Res.16 (1984) 125–127.
  60. IKEUCHI Masatoshi, YAGI Kinji, Pancreatic A cell generates action potential., 10.2170/jjphysiol.32.873
  61. Janjic, D., and Wollheim, C.B., Interactions of Ca2+, Mg2+ and Na+ in regulation of insulin release from rat islets. Am. J. Physiol.244 (1983) E222-E229.
  62. Kalkhoff, R.K., and Siegesmund, K.A., Fluctuations of calcium, phosphorus, sodium, potassium and chlorine in single alpha and beta cells during glucose perifusion of rat islets. J. clin. Invest.68 (1981) 517–524.
  63. Kawazu, S., Boschero, A.C., Delcroix, C., and Malaisse, W.J., The stimulus-secretion coupling of glucose-induced insulin release. Effect of glucose on Na+ fluxes in isolated islets. Pflügers Arch.375 (1978) 197–206.
  64. Lambert, A.E., The regulation of insulin secretion. Rev. Physiol. Biochem. Pharmac.75 (1976) 97–159.
  65. Lambert, A.E., Henquin, J.C., and Malvaux, P., Cationic environment and dynamics of insulin secretion. Effect of low concentrations of sodium. Endocrinology95 (1974) 1069–1077.
  66. Lebrun, P., Malaisse, W.J., and Herchuelz, A., Effect of calcium antagonists on potassium conductance in islet cells. Biochem. Pharmac.30 (1981) 3291–3294.
  67. Lebrun, P., Malaisse, W.J., and Herchuelz, A., Effect of the absence of bicarbonate upon intracellular pH and calcium fluxes in pancreatic islet cells. Biochim. biophys. Acta721 (1982) 357–365.
  68. Lebrun, P., Malaisse, W.J., and Herchuelz, A., Activation, but not inhibition, by glucose of Ca2+-dependent K+ permeability in the rat pancreatic B-cell. Biochim. biophys. Acta731 (1983) 145–150.
  69. Lebrun, P., Malaisse, W.J., and Herchuelz, A., Impairment by aminooxyacetate of ionic response to nutrients in pancreatic islets. Am. J. Physiol.245 (1983) E38-E46.
  70. Lindström P, Sehlin J, Effect of glucose on the intracellular pH of pancreatic islet cells, 10.1042/bj2180887
  71. Malaisse Willy J., Herchuelz André, Nutritional Regulation of K+ Conductance: An Unsettled Aspect of Pancreatic B Cell Physiology, Biochemical Actions of Hormones (1982) ISBN:9780124528093 p.69-92, 10.1016/b978-0-12-452809-3.50008-7
  72. Malaisse, W.J., Herchuelz, A., and Sener, A., Inorganic ions in insulin secretion, in: The islets of Langerhans-Biochemistry, Physiology and Pathology, pp. 149–171. Eds S.J. Cooperstein and D.T. Watkins. Academic Press, New York 1981.
  73. Malaisse, W.J., Hutton, J.C., Kawazu, S., Herchuelz, A., Valverde, I., and Sener, A., The stimulus-secretion coupling of glucose-induced insulin release. The links between metabolic and cationic events. Diabetologia16 (1979) 331–341.
  74. Malaisse W. J., Sener A., Herchuelz A., Effects of Insulinotropic Agents on Cationic Fluxes in Islet Cells, Treatment of EARLY DIABETES (1979) ISBN:9781461591122 p.85-96, 10.1007/978-1-4615-9110-8_14
  75. Marty, A. and Neher, E., Ionic channels in cultured rat pancreatic islet cells. J. Physiol.326 (1982) 36P-37P.
  76. Matthews, E.K., Dean, P.M., and Sakamoto, Y., The bioelectrical activity of the islet cell membrane, in: Insulin II, pp. 157–173. Eds A. Hasselblatt and F. v. Bruchausen. Springer Verlag, Berlin 1975.
  77. Matthews, E.K., and O'Connor, M.D.L., Dynamic oscillations in the membrane potential of pancreatic islet cells. J. exp. Biol.81 (1979) 75–91.
  78. Matthews E K, Sakamoto Y, Electrical characteristics of pancreatic islet cells., 10.1113/jphysiol.1975.sp010897
  79. Mattews E K, Sakamoto Y, Pancreatic islet cells: electrogenic and electrodiffusional control of membrane potential., 10.1113/jphysiol.1975.sp010898
  80. Meissner, H.P., Electrical characteristics of the beta-cells in pancreatic islets. J. Physiol., Paris72 (1976) 757–767.
  81. Meissner, H.P., and Atwater, I., The kinetics of electrical activity of beta cells in response to a square wave stimulation with glucose or glibenclamide. Horm. Metab. Res.8 (1976) 11–16.
  82. Meissner, H.P., and Henquin, J.C., Comparison of the effects of glucose, amino acids and sulphonamides on the membrane potential of pancreatic B-cells, in: Diabetes 1982, pp. 353–359. Ed. E.N. Mngola. Excerpta Medica, Amsterdam 1983.
  83. Meissner, H.P., and Henquin, J.C., The sodium pump of mouse pancreatic β-cells: electrogenic properties and activation by intracellular sodium, in: Electrogenic Transport: fundamental principles and physiological implications, pp. 295–306. Eds M.P. Blaustein and M. Lieberman. Raven Press, New York 1984.
  84. Meissner, H.P., Henquin, J.C., and Preissler, M., Potassium dependence of the membrane potential of pancreatic B cells. FEBS Lett.94 (1978) 87–89.
  85. Meissner H. P., Preissler M., Glucose-Induced Changes of the Membrane Potential of Pancreatic B-Cells: Their Significance for the Regulation of Insulin Release, Treatment of EARLY DIABETES (1979) ISBN:9781461591122 p.97-107, 10.1007/978-1-4615-9110-8_15
  86. Meissner, H.P., and Preissler, M., Ionic mechanisms of the glucose-induced membrane potential changes in B-cells. Horm. Metab. Res., suppl.10 (1980) 91–99.
  87. Meissner, H.P., Preissler, M., and Henquin, J.C., Possible ionic mechanisms of the electrical activity induced by glucose and tolbutamide in pancreatic B cells, in: Diabetes 1979, pp. 166–171. Ed. W.K. Waldhäusl. Excerpta Medica, Amsterdam 1980.
  88. Meissner Hans Peter, Schmeer Willi, THE SIGNIFICANCE OF CALCIUM IONS FOR THE GLUCOSE–INDUCED ELECTRICAL ACTIVITY OF PANCREATIC β–CELLS, The Mechanism of Gated Calcium Transport Across Biological Membranes (1981) ISBN:9780125249805 p.157-165, 10.1016/b978-0-12-524980-5.50024-7
  89. Meissner, H.P., and Schmelz, H., Membrane potential of beta cells in pancreatic islets. Pflügers Arch.351 (1974) 195–206.
  90. Meissner, H.P., and Schmidt, H., The electrical activity of pancreactic β-cells of diabetic mice. FEBS Lett.67 (1976) 371–374.
  91. Milner, R.D.G., and Hales, C.N., The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia3 (1967) 47–49.
  92. Milner R. D. G., Hales C. N., The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreasin vitro, 10.1042/bj1130473
  93. Pace, C.S., Activation of Na channels in islet cells: metabolic and secretory effects. Am. J. Physiol.237 (1979) E130-E135.
  94. Pace, C.S., Murphy, M., Conant, S., and Lacy, P.E., Somatostatin inhibition of glucose-induced electrical activity in cultured rat islet cells. Am. J. Physiol.233 (1977) C164-C171.
  95. Pace, C.S., and Smith, J.S., The role of chemiosmotic lysis in the exocytotic release of insulin. Endocrinology113 (1983) 964–969.
  96. Pace, C.S., Stillings, S.N., Hover, B.A., and Matschinsky, F.M., Electrical and secretory manifestations of glucose and amino acid interactions in rat pancreatic islets. Diabetes24 (1975) 489–496.
  97. Pace C. S., Tarvin J. T., Neighbors A. S., Pirkle J. A., Greider M. H., Use of a High Voltage Technique to Determine the Molecular Requirements for Exocytosis in Islet Cells, 10.2337/diab.29.11.911
  98. Pace, C.S., Tarvin, J.T., and Smith, J.S., Stimulus-secretion coupling in β-cells: modulation by pH. Am. J. Physiol.244 (1983) E3-E18.
  99. Pollard, H.B., Pazoles, C.J., and Creutz, C.E., Mechanism of calcium action and release of vesicle-bound hormones during exocytosis. Recent Prog. Horm. Res.37 (1981) 299–332.
  100. Ribalet, B., and Beigelman, P.M., Cyclic variation of K+ conductance in pancreatic β-cells: Ca2+ and voltage dependance. Am. J. Physiol.237 (1979) C137-C146.
  101. Ribalet, B., and Beigelman, P.M., Calcium action potentials and potassium permeability activation in pancreatic β-cells. Am. J. Physiol.239 (1980) C124-C133.
  102. Ribalet, B., and Beigelman, P.M., Effects of sodium on β-cell electrical activity. Am. J. Physiol.242 (1982) C296-C303.
  103. Richardson, B.P., Lowe, D.A., Donatsch, P., Taylor, P., and Stocklin, E., Na+ channels in pancreatic islet cells. Postgrad. med. J.57, suppl. 1 (1981) 98–109.
  104. Rorsman, P., Berggren, P.O., Gylfe, E., and Hellman, B., Reduction of the cytosolic calcium activity in clonal insulin-releasing cells exposed to glucose. Biosci. Rep.3 (1983) 939–946.
  105. Rosario, L.M., Alterations of potassium permeability in islets from hyperglycaemic ob/ob mice. Proceedings of the autumn meeting of the British Diabetic Association 1983, p.4.
  106. Santana De Sa Sonia, Ferrer Rosa, Rojas Eduardo, Atwater Illani, EFFECTS OF ADRENALINE AND NORADRENALINE ON GLUCOSE-INDUCED ELECTRICAL ACTIVITY OF MOUSE PANCREATIC β CELL, 10.1113/expphysiol.1983.sp002716
  107. Scott, A.M., Atwater, I., and Rojas, E., A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia21 (1981) 470–475.
  108. Sehlin, J., Interrelationship between chloride fluxes in pancreatic islets and insulin release. Am. J. Physiol.235 (1978) E501-E508.
  109. Sehlin, J., Univalent ions in islet cell function. Horm. Metab. Res., suppl.10 (1980) 73–80.
  110. Sehlin, J., Are Cl− mechanisms in mouse pancreatic islets involved in insulin release? Upsala J. med. Sci.86 (1981) 177–182.
  111. Sehlin, J., Transport systems of islet cells, in: The islets of Langerhans-Biochemistry, Physiology and Pathology, pp. 53–74. Eds S.J. Cooperstein, and D.T. Watkins. Academic Press, New York 1981.
  112. Sehlin, J., and Freinkel, N., Biphasic modulation of K+ permeability in pancreatic islets during acute stimulation with glucose. Diabetes32 (1983) 820–824.
  113. Sehlin J., Täljedal I.-B., Transport of rubidium and sodium in pancreatic islets, 10.1113/jphysiol.1974.sp010720
  114. Somers, G., Sener, A., Devis, G., and Malaisse, W.J., The stimulus-secretion coupling of glucose-induced insulin release. The anion-osmotic hypothesis for exocytosis. Pflügers Arch.388 (1980) 249–253.
  115. Stagner, J.I., Samols, E., and Weir, G.C., Sustained oscillations of insulin, glucagon and somatostatin from the isolated canine pancreas during exposure to a constant glucose concentration. J. clin. Invest.65 (1980) 939–942.
  116. Tamagawa, T., and Henquin, J.C., Chloride modulation of insulin release,86Rb+ efflux, and45Ca2+ fluxes in rat islets stimulated by various secretagogues. Diabetes32 (1983) 416–423.
  117. Tarvin, J.T., and Pace, C.S., Glucose-induced electrical activity in the pancreatic β-cell: effect of veratridine. Am. J. Physiol.240 (1981) C127-C134.
  118. Trus, M., Warner, H., and Matschinsky, F., Effect of glucose on insulin release and on intermediary metabolism of isolated perifused pancreatic islets from fed and fasted rats. Diabetes29 (1980) 1–14.
  119. Wollheim, C.B., and Sharp, G.W.G., The regulation of insulin release by calcium. Physiol. Rev.61 (1981) 914–973.
  120. Yaseen, M.A., Smith, J.E., Doolabh, N., and Howell, S.L., Insulin secretion by exocytosis from permeabilized islets of Langerhans. Diabetologia25 (1983) 205 (Abstract).