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Dehghany, J.* ; Hoboth, P. ; Ivanova, A. ; Mziaut, H. ; Müller, A. ; Kalaidzidis, Y.* ; Solimena, M. ; Meyer-Hermann, M.*

A spatial model of insulin-granule dynamics in pancreatic β-cells.

Traffic 16, 797-813 (2015)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Insulin secretion from pancreatic β-cells in response to sudden glucose stimulation is biphasic. Prolonged secretion in vivo requires synthesis, delivery to the plasma membrane (PM) and exocytosis of insulin secretory granules (SGs). Here, we provide the first agent-based space-resolved model for SG dynamics in pancreatic β-cells. Using recent experimental data, we consider a single β-cell with identical SGs moving on a phenomenologically represented cytoskeleton network. A single exocytotic machinery mediates SG exocytosis on the PM. This novel model reproduces the measured spatial organization of SGs and insulin secretion patterns under different stimulation protocols. It proposes that the insulin potentiation effect and the rising second-phase secretion are mainly due to the increasing number of docking sites on the PM. Furthermore, it shows that 6 min after glucose stimulation, the 'newcomer' SGs are recruited from a region within less than 600 nm from the PM.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Agent-based Model ; Biphasic Insulin Secretion ; Diabetes ; Granule Dynamics ; Newcomer ; Potentiation ; β-cell; Type-2 Diabetes-mellitus; Beta-cells; Secretory Granules; B-cells; Intracellular Degradation; Docked Granules; Ca2+ Channels; In-vivo; Glucose; Exocytosis
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1398-9219
e-ISSN 1600-0854
Zeitschrift Traffic
Quellenangaben Band: 16, Heft: 8, Seiten: 797-813 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502600-001
PubMed ID 25809669
DOI 10.1111/tra.12286
WOS ID WOS:000357683900001
Erfassungsdatum 2015-05-18
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