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Diabetes 51:S74-S82, 2002
© 2002 by the American Diabetes Association, Inc.

Section 2: Biphasic Insulin Release: Pools and Signal Modulation

A Subset of 50 Secretory Granules in Close Contact With L-Type Ca2+ Channels Accounts for First-Phase Insulin Secretion in Mouse ß-Cells

Sebastian Barg, Lena Eliasson, Erik Renström, and Patrik Rorsman

From the Department of Molecular and Cellular Physiology, Institute of Physiology, Lund University, Lund, Sweden

Capacitance measurements were applied to mouse pancreatic ß-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only <50 of the ß-cell’s >10,000 granules are immediately available for release. The releasable granules tightly associate with the voltage-gated {alpha}1C Ca2+ channels, and it is proposed that the release of these granules accounts for first-phase insulin secretion. Subsequent replenishment of the releasable pool by priming of previously nonreleasable granules is required for second-phase insulin secretion. The latter reaction depends on intragranular acidification due to the concerted action of granular bafilomycin-sensitive v-type H+-ATPase and 4,4-diisothiocyanostilbene-2,2-disulfonate–blockable ClC-3 Cl- channels. Lowering the cytoplasmic ATP/ADP ratio prevents granule acidification, granule priming, and refilling of the releasable pool. The latter finding provides an explanation to the transient nature of insulin secretion elicited by, for example, high extracellular K+ in the absence of metabolizable fuels.


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