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) All Versions of this Article: 586/14/3313    most recent jphysiol.2008.155317v1 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 Google Scholar Articles by Eliasson, L. Articles by Rorsman, P. PubMed PubMed Citation Articles by Eliasson, L. Articles by Rorsman, P. Related Collections Review articles Cellular

¹ Department of Clinical Sciences in Malmö, Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Clinical Research Centre, Malmö SE-205 02, Sweden
² Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK
³ Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil

Pancreatic β-cells secrete insulin by Ca²⁺-dependent exocytosis of secretory granules. β-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca²⁺ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in β-cells in intact islets indicate a release rate of 15 granules per β-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is 1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long-term exposure to lipids.

(Received 16 April 2008; accepted after revision 21 May 2008; first published online 29 May 2008)
Corresponding author P. Rorsman: OCDEM, University of Oxford, Oxford OX3 7LJ, UK. Email: patrik.rorsman{at}ocdem.ox.ac.uk