Mechanisms of biphasic insulin-granule exocytosis – roles of the cytoskeleton, small GTPases and SNARE proteins
Author:
Wang Zhanxiang1, Thurmond Debbie C.1
Affiliation:
1. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Abstract
The release of insulin from pancreatic islets requires negative regulation to ensure low levels of insulin release under resting conditions, as well as positive regulation to facilitate robust responsiveness to conditions of elevated fuel or glucose. The first phase of release involves the plasma-membrane fusion of a small pool of granules, termed the readily releasable pool; these granules are already at the membrane under basal conditions, and discharge their cargo in response to nutrient and also non-nutrient secretagogues. By contrast, second-phase secretion is evoked exclusively by nutrients, and involves the mobilization of intracellular granules to t-SNARE sites at the plasma membrane to enable the distal docking and fusion steps of insulin exocytosis. Nearly 40 years ago, the actin cytoskeleton was first recognized as a key mediator of biphasic insulin release, and was originally presumed to act as a barrier to block granule docking at the cell periphery. More recently, however, the discovery of cycling GTPases that are involved in F-actin reorganization in the islet β-cell, combined with the availability of reagents that are more specific and tools with which to study the mechanisms that underlie granule movement, have contributed greatly to our understanding of the role of the cytoskeleton in regulating biphasic insulin secretion. Herein, we provide historical perspective and review recent progress that has been made towards integrating cytoskeletal reorganization and cycling of small Rho-, Rab- and Ras-family GTPases into our current models of stimulus-secretion coupling and second-phase insulin release.
Publisher
The Company of Biologists
Reference168 articles.
1. Asahara, S., Kido, Y., Shigeyama, T., Matsuda, T., Takeda, A., Inoue, T., Shibutani, Y., Koyanagi, M., Uchida, T. and Kasuga, M. (2008). Rac1 regulates glucose-induced insulin secretion through modulation of cytoskeleton organization in beta cells. Diabetes57, Suppl. 1, A55. 2. Balczon, R., Overstreet, K. A., Zinkowski, R. P., Haynes, A. and Appel, M. (1992). The identification, purification, and characterization of a pancreatic beta-cell form of the microtubule adenosine triphosphatase kinesin. Endocrinology131, 331-336. 3. Barg, S., Huang, P., Eliasson, L., Nelson, D. J., Obermuller, S., Rorsman, P., Thevenod, F. and Renstrom, E. (2001). Priming of insulin granules for exocytosis by granular Cl(-) uptake and acidification. J. Cell Sci.114, 2145-2154. 4. Barg, S., Eliasson, L., Renstrom, E. and Rorsman, P. (2002). A subset of 50 secretory granules in close contact with L-type Ca(2+) channels accounts for first-phase insulin secretion in mouse beta-cells. Diabetes51, S74-S82. 5. Berglund, O. (1980). Different dynamics of insulin secretion in the perfused pancreas of mouse and rat. Acta Endocrinol.93, 54-60.
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