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. 1994 Feb 1;297(Pt 3):455–461. doi: 10.1042/bj2970455

Two sites of glucose control of insulin release with distinct dependence on the energy state in pancreatic B-cells.

P Detimary 1, P Gilon 1, M Nenquin 1, J C Henquin 1
PMCID: PMC1137855  PMID: 8110181

Abstract

The energy state of pancreatic B-cells may influence insulin release at several steps of stimulus-secretion coupling. By closing ATP-sensitive K+ channels (K(+)-ATP channels), a rise in the ATP/ADP ratio may regulate the membrane potential, and hence Ca2+ influx. It may also modulate the effectiveness of Ca2+ on its intracellular targets. To assess the existence of these two roles and determine their relative importance for insulin release, we tested the effects of azide, a mitochondrial poison, on mouse B-cell function under various conditions. During stimulation by glucose alone, when K(+)-ATP channels are controlled by cellular metabolism, azide caused parallel, concentration-dependent (0.5-5 mM), membrane repolarization, decrease in cytosolic Ca2+ concentration [Ca2+]i and inhibition of insulin release. When K(+)-ATP channels were closed pharmacologically (by tolbutamide in high glucose), azide did not repolarize the membrane or decrease [Ca2+]i, and was much less effective in inhibiting insulin release. A similar resistance to azide was observed when K(+)-ATP channels were opened by diazoxide, and high K+ was used to depolarize the membrane and raise [Ca2+]i. In contrast, azide similarly decreased ATP levels and increased ADP levels, thereby lowering the ATP/ADP ratio under all conditions. In conclusion, lowering the ATP/ADP ratio in B-cells can inhibit insulin release even when [Ca2+]i remains high. However, this distal step is much more resistant to a decrease in the energy state of B-cells than is the control of membrane potential by K(+)-ATP channels. Generation of the signal triggering insulin release, high [Ca2+]i, through metabolic control of membrane potential requires a higher global ATP/ADP ratio than does activation of the secretory process itself.

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Selected References

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  1. Aleyassine H. Energy requirements for insulin release from rat pancreas in vitro. Endocrinology. 1970 Jul;87(1):84–89. doi: 10.1210/endo-87-1-84. [DOI] [PubMed] [Google Scholar]
  2. Ali L., Grapengiesser E., Gylfe E., Hellman B., Lund P. E. Free and bound sodium in pancreatic beta-cells exposed to glucose and tolbutamide. Biochem Biophys Res Commun. 1989 Oct 16;164(1):212–218. doi: 10.1016/0006-291x(89)91704-x. [DOI] [PubMed] [Google Scholar]
  3. Ashcroft F. M., Rorsman P. Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol. 1989;54(2):87–143. doi: 10.1016/0079-6107(89)90013-8. [DOI] [PubMed] [Google Scholar]
  4. Ashcroft S. J., Weerasinghe L. C., Randle P. J. Interrelationship of islet metabolism, adenosine triphosphate content and insulin release. Biochem J. 1973 Feb;132(2):223–231. doi: 10.1042/bj1320223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Atwater I., Dawson C. M., Ribalet B., Rojas E. Potassium permeability activated by intracellular calcium ion concentration in the pancreatic beta-cell. J Physiol. 1979 Mar;288:575–588. [PMC free article] [PubMed] [Google Scholar]
  6. Bozem M., Henquin J. C. Glucose modulation of spike activity independently from changes in slow waves of membrane potential in mouse B-cells. Pflugers Arch. 1988 Dec;413(2):147–152. doi: 10.1007/BF00582524. [DOI] [PubMed] [Google Scholar]
  7. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J. 1964 Oct;93(1):66–78. doi: 10.1042/bj0930066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dean P. M., Matthews E. K. Glucose-induced electrical activity in pancreatic islet cells. J Physiol. 1970 Sep;210(2):255–264. doi: 10.1113/jphysiol.1970.sp009207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Draznin B. Intracellular calcium, insulin secretion, and action. Am J Med. 1988 Nov 28;85(5A):44–58. doi: 10.1016/0002-9343(88)90397-x. [DOI] [PubMed] [Google Scholar]
  10. Dunne M. J., Petersen O. H. Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. Biochim Biophys Acta. 1991 Mar 7;1071(1):67–82. doi: 10.1016/0304-4157(91)90012-l. [DOI] [PubMed] [Google Scholar]
  11. Escolar J. C., Hoo-Paris R., Castex C., Sutter B. C. Effect of low temperatures on glucose-induced insulin secretion and glucose metabolism in isolated pancreatic islets of the rat. J Endocrinol. 1990 Apr;125(1):45–51. doi: 10.1677/joe.0.1250045. [DOI] [PubMed] [Google Scholar]
  12. Gembal M., Detimary P., Gilon P., Gao Z. Y., Henquin J. C. Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K+ channels in mouse B cells. J Clin Invest. 1993 Mar;91(3):871–880. doi: 10.1172/JCI116308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gembal M., Gilon P., Henquin J. C. Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells. J Clin Invest. 1992 Apr;89(4):1288–1295. doi: 10.1172/JCI115714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gillis K. D., Gee W. M., Hammoud A., McDaniel M. L., Falke L. C., Misler S. Effects of sulfonamides on a metabolite-regulated ATPi-sensitive K+ channel in rat pancreatic B-cells. Am J Physiol. 1989 Dec;257(6 Pt 1):C1119–C1127. doi: 10.1152/ajpcell.1989.257.6.C1119. [DOI] [PubMed] [Google Scholar]
  15. Gilon P., Henquin J. C. Activation of muscarinic receptors increases the concentration of free Na+ in mouse pancreatic B-cells. FEBS Lett. 1993 Jan 11;315(3):353–356. doi: 10.1016/0014-5793(93)81193-4. [DOI] [PubMed] [Google Scholar]
  16. Gilon P., Henquin J. C. Influence of membrane potential changes on cytoplasmic Ca2+ concentration in an electrically excitable cell, the insulin-secreting pancreatic B-cell. J Biol Chem. 1992 Oct 15;267(29):20713–20720. [PubMed] [Google Scholar]
  17. Henquin J. C. Adenosine triphosphate-sensitive K+ channels may not be the sole regulators of glucose-induced electrical activity in pancreatic B-cells. Endocrinology. 1992 Jul;131(1):127–131. doi: 10.1210/endo.131.1.1611991. [DOI] [PubMed] [Google Scholar]
  18. Henquin J. C. D-glucose inhibits potassium efflux from pancreatic islet cells. Nature. 1978 Jan 19;271(5642):271–273. doi: 10.1038/271271a0. [DOI] [PubMed] [Google Scholar]
  19. Henquin J. C., Meissner H. P. Opposite effects of tolbutamide and diazoxide on 86Rb+ fluxes and membrane potential in pancreatic B cells. Biochem Pharmacol. 1982 Apr 1;31(7):1407–1415. doi: 10.1016/0006-2952(82)90036-3. [DOI] [PubMed] [Google Scholar]
  20. Henquin J. C., Meissner H. P. Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells. Experientia. 1984 Oct 15;40(10):1043–1052. doi: 10.1007/BF01971450. [DOI] [PubMed] [Google Scholar]
  21. Henquin J. C., Meissner H. P. The electrogenic sodium-potassium pump of mouse pancreatic B-cells. J Physiol. 1982 Nov;332:529–552. doi: 10.1113/jphysiol.1982.sp014429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Henquin J. C. Opposite effects of intracellular Ca2+ and glucose on K+ permeability of pancreatic islet cells. Nature. 1979 Jul 5;280(5717):66–68. doi: 10.1038/280066a0. [DOI] [PubMed] [Google Scholar]
  23. Hopkins W. F., Fatherazi S., Peter-Riesch B., Corkey B. E., Cook D. L. Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic beta-cells and HIT cells. J Membr Biol. 1992 Sep;129(3):287–295. doi: 10.1007/BF00232910. [DOI] [PubMed] [Google Scholar]
  24. Jones P. M., Stutchfield J., Howell S. L. Effects of Ca2+ and a phorbol ester on insulin secretion from islets of Langerhans permeabilised by high-voltage discharge. FEBS Lett. 1985 Oct 21;191(1):102–106. doi: 10.1016/0014-5793(85)81002-4. [DOI] [PubMed] [Google Scholar]
  25. Malaisse W., Malaisse-Lagae F., Wright P. H. A new method for the measurement in vitro of pancreatic insulin secretion. Endocrinology. 1967 Jan;80(1):99–108. doi: 10.1210/endo-80-1-99. [DOI] [PubMed] [Google Scholar]
  26. Meissner H. P. Membrane potential measurements in pancreatic beta cells with intracellular microelectrodes. Methods Enzymol. 1990;192:235–246. doi: 10.1016/0076-6879(90)92073-m. [DOI] [PubMed] [Google Scholar]
  27. Milner R. D., Hales C. N. The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro. Biochem J. 1969 Jul;113(3):473–479. doi: 10.1042/bj1130473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Misler S., Barnett D. W., Falke L. C. Effects of metabolic inhibition by sodium azide on stimulus-secretion coupling in B cells of human islets of Langerhans. Pflugers Arch. 1992 Jun;421(2-3):289–291. doi: 10.1007/BF00374842. [DOI] [PubMed] [Google Scholar]
  29. Misler S., Gee W. M., Gillis K. D., Scharp D. W., Falke L. C. Metabolite-regulated ATP-sensitive K+ channel in human pancreatic islet cells. Diabetes. 1989 Apr;38(4):422–427. doi: 10.2337/diab.38.4.422. [DOI] [PubMed] [Google Scholar]
  30. Niki I., Ashcroft F. M., Ashcroft S. J. The dependence on intracellular ATP concentration of ATP-sensitive K-channels and of Na,K-ATPase in intact HIT-T15 beta-cells. FEBS Lett. 1989 Nov 6;257(2):361–364. doi: 10.1016/0014-5793(89)81572-8. [DOI] [PubMed] [Google Scholar]
  31. Ohta M., Nelson D., Nelson J., Meglasson M. D., Erecińska M. Oxygen and temperature dependence of stimulated insulin secretion in isolated rat islets of Langerhans. J Biol Chem. 1990 Oct 15;265(29):17525–17532. [PubMed] [Google Scholar]
  32. 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. Diabetes. 1980 Nov;29(11):911–918. doi: 10.2337/diab.29.11.911. [DOI] [PubMed] [Google Scholar]
  33. Prentki M., Matschinsky F. M. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol Rev. 1987 Oct;67(4):1185–1248. doi: 10.1152/physrev.1987.67.4.1185. [DOI] [PubMed] [Google Scholar]
  34. Rajan A. S., Aguilar-Bryan L., Nelson D. A., Yaney G. C., Hsu W. H., Kunze D. L., Boyd A. E., 3rd Ion channels and insulin secretion. Diabetes Care. 1990 Mar;13(3):340–363. doi: 10.2337/diacare.13.3.340. [DOI] [PubMed] [Google Scholar]
  35. Schmid-Antomarchi H., De Weille J., Fosset M., Lazdunski M. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells. J Biol Chem. 1987 Nov 25;262(33):15840–15844. [PubMed] [Google Scholar]
  36. Trube G., Rorsman P., Ohno-Shosaku T. Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells. Pflugers Arch. 1986 Nov;407(5):493–499. doi: 10.1007/BF00657506. [DOI] [PubMed] [Google Scholar]
  37. Vallar L., Biden T. J., Wollheim C. B. Guanine nucleotides induce Ca2+-independent insulin secretion from permeabilized RINm5F cells. J Biol Chem. 1987 Apr 15;262(11):5049–5056. [PubMed] [Google Scholar]
  38. Wolf B. A., Colca J. R., Turk J., Florholmen J., McDaniel M. L. Regulation of Ca2+ homeostasis by islet endoplasmic reticulum and its role in insulin secretion. Am J Physiol. 1988 Feb;254(2 Pt 1):E121–E136. doi: 10.1152/ajpendo.1988.254.2.E121. [DOI] [PubMed] [Google Scholar]

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