Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

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

Bruton, J.D. and Lemmens, R. and Shi, C.L. and Persson-Sjogren, H. and Westerblad, H. and Ahmed, M. and Pyne, N.J. and Frame, M.J. and Furman, B.L. and Islam, M.S. (2003) Ryanodine receptors of pancreatic beta-cells mediate a distinct context-dependent signal for insulin secretion. FASEB Journal, 17. pp. 301-303. ISSN 0892-6638

Full text not available in this repository. (Request a copy from the Strathclyde author)

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.

Item type: Article
ID code: 37877
Keywords: pancreatic beta-cells , insulin secretion , ryanodine receptors, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
Strathclyde Business School > Human Resource Management
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 24 Feb 2012 15:11
    Last modified: 04 Oct 2012 12:28
    URI: http://strathprints.strath.ac.uk/id/eprint/37877

    Actions (login required)

    View Item