Dataset Information

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

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.

SUBMITTER: Low JT

PROVIDER: S-EPMC3825531 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Low Jiun T JT Mitchell Justin M JM Do Oanh H OH Bax Jacinda J Rawlings Alicia A Zavortink Michael M Morgan Garry G Parton Robert G RG Gaisano Herbert Y HY Thorn Peter P

Diabetologia 20130901 12

<h4>Aims/hypothesis</h4>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 de ...[more]

PMID: 23995471

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Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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

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