HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tamarina, N. A. Articles by Philipson, L. H. Search for Related Content PubMed PubMed Citation Articles by Tamarina, N. A. Articles by Philipson, L. H. Social Bookmarking                What's this?

Inositol (1,4,5)-Trisphosphate Dynamics and Intracellular Calcium Oscillations in Pancreatic ß-Cells

¹ Department of Medicine, University of Chicago, Chicago, Illinois
² Pacific Northwest Research Institute, Seattle, Washington

Glucose-stimulated insulin secretion is associated with transients of intracellular calcium concentration ([Ca²⁺]_i) in the pancreatic ß-cell. We tested the hypothesis that inositol (1,4,5)-trisphosphate [Ins(1,4,5)P₃] [Ca²⁺]_i release is incorporated in glucose-induced [Ca²⁺]_i oscillations in mouse islets and MIN6 cells. We found that depletion of intracellular Ca²⁺ stores with thapsigargin increased the oscillation frequency by twofold and inhibited the slow recovery phase of [Ca²⁺]_i oscillations. We employed a pleckstrin homology domain–containing fluorescent biosensor, phospholipase C pleckstrin homology domain–enhanced green fluorescent protein, to visualize Ins(1,4,5)P₃ dynamics in insulin-secreting MIN6 cells and mouse islets in real time using a video-rate confocal system. In both types of cells, stimulation with carbamoylcholine (CCh) and depolarization with KCl results in an increase in Ins(1,4,5)P₃ accumulation in the cytoplasm. When stimulated with glucose, the Ins(1,4,5)P₃ concentration in the cytoplasm oscillates in parallel with oscillations of [Ca²⁺]_i. Maximal accumulation of Ins(1,4,5)P₃ in these oscillations coincides with the peak of [Ca²⁺]_i and tracks changes in frequencies induced by the voltage-gated K⁺ channel blockade. We show that Ins(1,4,5)P₃ release in insulin-secreting cells can be stimulated by depolarization-induced Ca²⁺ flux. We conclude that Ins(1,4,5)P₃ concentration oscillates in parallel with [Ca²⁺]_i in response to glucose stimulation, but it is not the driving force for [Ca²⁺]_i oscillations.

Abbreviations: ATP, adenosine 5'-triphosphate; [Ca²⁺]_i, intracellular calcium concentration; CCh, carbamoylcholine; EGFP, enhanced green fluorescent protein; Ins(1,4,5)P₃, inositol (1,4,5)-trisphosphate; KRBB, Krebs-Ringer bicarbonate buffer; LSCM, laser scanning confocal microscope; PHD, pleckstrin homology domain; PIP₂, phosphatidylinositol(4,5)-bisphosphate; PLC, phospholipase C; TEA, tetraethylammonium

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. A. Jacobson, C. R. Weber, S. Bao, J. Turk, and L. H. Philipson Modulation of the Pancreatic Islet beta-Cell-delayed Rectifier Potassium Channel Kv2.1 by the Polyunsaturated Fatty Acid Arachidonate J. Biol. Chem., March 9, 2007; 282(10): 7442 - 7449. [Abstract] [Full Text] [PDF]

				S. Thore, A. Wuttke, and A. Tengholm Rapid Turnover of Phosphatidylinositol-4,5-Bisphosphate in Insulin-Secreting Cells Mediated by Ca2+ and the ATP-to-ADP Ratio Diabetes, March 1, 2007; 56(3): 818 - 826. [Abstract] [Full Text] [PDF]