Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion

J.D. Bruton, R. Lemmens, C.L. Shi, H. Persson-Sjogren, H. Westerblad, M. Ahmed, N.J. Pyne, M.J. Frame, B.L. Furman, M.S. Islam

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The ryanodine (RY) receptors in β-cells amplify signals by Ca2+-induced Ca
2+ release (CICR). The role of CICR in insulin secretion remains unclear in spite of the fact that caffeine is known to stimulate secretion. This effect of caffeine is attributed solely to the inhibition of cAMPphosphodiesterases (cAMP-PDEs). We demonstrate that stimulation of insulin secretion by caffeine is due to a sensitization of the RY receptors. The dose-response relationship of caffeineinduced inhibition of cAMP-PDEs was not correlated with the stimulation of insulin secretion. Sensitization of the RY receptors stimulated insulin secretion in a context-dependent manner, that is, only in the presence of a high concentration of glucose. This effect of caffeine depended on an increase in [Ca2+]i. Confocal images of β-cells demonstrated an increase in [Ca2+]iinduced by caffeine but not by forskolin. 9-Methyl-7-bromoeudistomin D (MBED), which sensitizes RY receptors, did not inhibit cAMP-PDEs, but it stimulated secretion in a glucose-dependent manner. The stimulation of secretion by caffeine and MBED involved both the first and the second phases of secretion. We conclude that the RY receptors of β-cells mediate a distinct glucose-dependent signal for insulin secretion and may be a target for developing drugs that will stimulate insulin secretion only in a glucose-dependent manner.
LanguageEnglish
Pages301-303
Number of pages3
JournalFASEB Journal
Volume17
DOIs
Publication statusPublished - 2003

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Ryanodine Receptor Calcium Release Channel
Insulin-Secreting Cells
Caffeine
Insulin
Glucose
Colforsin
Pharmaceutical Preparations

Keywords

  • pancreatic beta-cells
  • insulin secretion
  • ryanodine receptors

Cite this

Bruton, J. D., Lemmens, R., Shi, C. L., Persson-Sjogren, H., Westerblad, H., Ahmed, M., ... Islam, M. S. (2003). Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion. FASEB Journal, 17, 301-303. https://doi.org/10.1096/fj.02-0481fje
Bruton, J.D. ; Lemmens, R. ; Shi, C.L. ; Persson-Sjogren, H. ; Westerblad, H. ; Ahmed, M. ; Pyne, N.J. ; Frame, M.J. ; Furman, B.L. ; Islam, M.S. / Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion. In: FASEB Journal. 2003 ; Vol. 17. pp. 301-303.
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Bruton, JD, Lemmens, R, Shi, CL, Persson-Sjogren, H, Westerblad, H, Ahmed, M, Pyne, NJ, Frame, MJ, Furman, BL & Islam, MS 2003, 'Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion' FASEB Journal, vol. 17, pp. 301-303. https://doi.org/10.1096/fj.02-0481fje

Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion. / Bruton, J.D.; Lemmens, R.; Shi, C.L.; Persson-Sjogren, H.; Westerblad, H.; Ahmed, M.; Pyne, N.J.; Frame, M.J.; Furman, B.L.; Islam, M.S.

In: FASEB Journal, Vol. 17, 2003, p. 301-303.

Research output: Contribution to journalArticle

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T1 - Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion

AU - Bruton, J.D.

AU - Lemmens, R.

AU - Shi, C.L.

AU - Persson-Sjogren, H.

AU - Westerblad, H.

AU - Ahmed, M.

AU - Pyne, N.J.

AU - Frame, M.J.

AU - Furman, B.L.

AU - Islam, M.S.

PY - 2003

Y1 - 2003

N2 - The ryanodine (RY) receptors in β-cells amplify signals by Ca2+-induced Ca2+ release (CICR). The role of CICR in insulin secretion remains unclear in spite of the fact that caffeine is known to stimulate secretion. This effect of caffeine is attributed solely to the inhibition of cAMPphosphodiesterases (cAMP-PDEs). We demonstrate that stimulation of insulin secretion by caffeine is due to a sensitization of the RY receptors. The dose-response relationship of caffeineinduced inhibition of cAMP-PDEs was not correlated with the stimulation of insulin secretion. Sensitization of the RY receptors stimulated insulin secretion in a context-dependent manner, that is, only in the presence of a high concentration of glucose. This effect of caffeine depended on an increase in [Ca2+]i. Confocal images of β-cells demonstrated an increase in [Ca2+]iinduced by caffeine but not by forskolin. 9-Methyl-7-bromoeudistomin D (MBED), which sensitizes RY receptors, did not inhibit cAMP-PDEs, but it stimulated secretion in a glucose-dependent manner. The stimulation of secretion by caffeine and MBED involved both the first and the second phases of secretion. We conclude that the RY receptors of β-cells mediate a distinct glucose-dependent signal for insulin secretion and may be a target for developing drugs that will stimulate insulin secretion only in a glucose-dependent manner.

AB - The ryanodine (RY) receptors in β-cells amplify signals by Ca2+-induced Ca2+ release (CICR). The role of CICR in insulin secretion remains unclear in spite of the fact that caffeine is known to stimulate secretion. This effect of caffeine is attributed solely to the inhibition of cAMPphosphodiesterases (cAMP-PDEs). We demonstrate that stimulation of insulin secretion by caffeine is due to a sensitization of the RY receptors. The dose-response relationship of caffeineinduced inhibition of cAMP-PDEs was not correlated with the stimulation of insulin secretion. Sensitization of the RY receptors stimulated insulin secretion in a context-dependent manner, that is, only in the presence of a high concentration of glucose. This effect of caffeine depended on an increase in [Ca2+]i. Confocal images of β-cells demonstrated an increase in [Ca2+]iinduced by caffeine but not by forskolin. 9-Methyl-7-bromoeudistomin D (MBED), which sensitizes RY receptors, did not inhibit cAMP-PDEs, but it stimulated secretion in a glucose-dependent manner. The stimulation of secretion by caffeine and MBED involved both the first and the second phases of secretion. We conclude that the RY receptors of β-cells mediate a distinct glucose-dependent signal for insulin secretion and may be a target for developing drugs that will stimulate insulin secretion only in a glucose-dependent manner.

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KW - insulin secretion

KW - ryanodine receptors

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DO - 10.1096/fj.02-0481fje

M3 - Article

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SP - 301

EP - 303

JO - FASEB Journal

T2 - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

ER -