Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell

Low, Jiun T., Mitchell, Justin M., Do, Oanh H., Bax, Jacinda, Rawlings, Alicia, Zavortink, Michael, Garry Morgan, Parton, Robert G., Gaisano, Herbert Y. and Thorn, Peter (2013) Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell. Diabetologia, 56 12: 2629-2637. doi:10.1007/s00125-013-3019-5

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Author Low, Jiun T.
Mitchell, Justin M.
Do, Oanh H.
Bax, Jacinda
Rawlings, Alicia
Zavortink, Michael
Garry Morgan
Parton, Robert G.
Gaisano, Herbert Y.
Thorn, Peter
Title Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
1432-0428
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00125-013-3019-5
Open Access Status DOI
Volume 56
Issue 12
Start page 2629
End page 2637
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract In dispersed single beta cells the response of each cell to glucose is heterogeneous. In contrast, within an islet, cell-to-cell communication leads to glucose inducing a more homogeneous response. For example, increases in NAD(P)H and calcium are relatively uniform across the cells of the islet. These data suggest that secretion of insulin from single beta cells within an islet should also be relatively homogeneous. The aim of this study was to test this hypothesis by determining the glucose dependence of single-cell insulin responses within an islet.
Formatted abstract
Aims/hypothesis In dispersed single beta cells the response of each cell to glucose is heterogeneous. In contrast, within an islet, cell-to-cell communication leads to glucose inducing a more homogeneous response. For example, increases in NAD(P)H and calcium are relatively uniform across the cells of the islet. These data suggest that secretion of insulin from single beta cells within an islet should also be relatively homogeneous. The aim of this study was to test this hypothesis by determining the glucose dependence of single-cell insulin responses within an islet.

Methods Two-photon microscopy was used to detect the glucose-induced fusion of single insulin granules within beta cells in intact mouse islets.

Results First, we validated our assay and showed that the measures of insulin secretion from whole islets could be explained by the time course and numbers of granule fusion events observed. Subsequent analysis of the patterns of granule fusion showed that cell recruitment is a significant factor, accounting for a fourfold increase from 3 to 20 mmol/l glucose. However, the major factor is the regulation of the numbers of granule fusion events within each cell, which increase ninefold over the range of 3 to 20 mmol/l glucose. Further analysis showed that two types of granule fusion event occur: ‘full fusion’ and ‘kiss and run’. We show that the relative frequency of each type of fusion is independent of glucose concentration and is therefore not a factor in the control of insulin secretion.

Conclusions/interpretation Within an islet, glucose exerts its main effect through increasing the numbers of insulin granule fusion events within a cell.
Keyword Insulin
Islet
Secretion
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP110100642
APP1002520
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 22 Nov 2013, 21:48:10 EST by Susan Allen on behalf of School of Biomedical Sciences