Insulin Secretory Granules Enter a Highly Calcium-Sensitive State following Palmitate-Induced Dissociation from Calcium Channels: A Theoretical Study
(2010) In Journal of Neuroendocrinology 22(12). p.1315-1324- Abstract
- Impaired insulin secretion is a major contributor to diabetes. Obesity is a known risk factor for the development of diabetes, and prolonged exposure of pancreatic islets to lipids results in impaired insulin secretion. Insulin is released from pancreatic beta-cells as a result of Ca2+-induced exocytosis. Recent experiments have shown that chronic palmitate exposure results in the loss of localised Ca2+-influx and impaired exocytosis of insulin secretory granules in beta-cells. In the present study, the roles of Ca2+-channel clustering disruption, and dissociation of granules from Ca2+-channels, in the impaired exocytotic and secretory responses from palmitate-treated beta-cells, are investigated using mathematical models of Ca2+ dynamics,... (More)
- Impaired insulin secretion is a major contributor to diabetes. Obesity is a known risk factor for the development of diabetes, and prolonged exposure of pancreatic islets to lipids results in impaired insulin secretion. Insulin is released from pancreatic beta-cells as a result of Ca2+-induced exocytosis. Recent experiments have shown that chronic palmitate exposure results in the loss of localised Ca2+-influx and impaired exocytosis of insulin secretory granules in beta-cells. In the present study, the roles of Ca2+-channel clustering disruption, and dissociation of granules from Ca2+-channels, in the impaired exocytotic and secretory responses from palmitate-treated beta-cells, are investigated using mathematical models of Ca2+ dynamics, granule pools, exocytosis and secretion. It is shown that either disruption of Ca2+-channel clusters or dissociation of granules from Ca2+-channels with a shift to a highly calcium-sensitive pool can explain the recent experimental findings of palmitate-induced defects of exocytosis and insulin secretion. On the basis of imaging results, it is argued that a shift to a highly calcium-sensitive state after dissociation of granules from Ca2+-channels is the most likely explanation for the experimental findings from beta-cells exposed chronically to palmitate. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1868064
- author
- Pedersen, Morten Gram LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- HCSP, palmitate, insulin secretion, beta-cells, mathematical modelling
- in
- Journal of Neuroendocrinology
- volume
- 22
- issue
- 12
- pages
- 1315 - 1324
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000284425700011
- scopus:78649495783
- ISSN
- 0953-8194
- DOI
- 10.1111/j.1365-2826.2010.02056.x
- language
- English
- LU publication?
- yes
- id
- 28e24c3a-fd21-4005-aba9-7f12d2f342b7 (old id 1868064)
- date added to LUP
- 2016-04-01 12:57:46
- date last changed
- 2022-01-27 08:34:50
@article{28e24c3a-fd21-4005-aba9-7f12d2f342b7,
abstract = {{Impaired insulin secretion is a major contributor to diabetes. Obesity is a known risk factor for the development of diabetes, and prolonged exposure of pancreatic islets to lipids results in impaired insulin secretion. Insulin is released from pancreatic beta-cells as a result of Ca2+-induced exocytosis. Recent experiments have shown that chronic palmitate exposure results in the loss of localised Ca2+-influx and impaired exocytosis of insulin secretory granules in beta-cells. In the present study, the roles of Ca2+-channel clustering disruption, and dissociation of granules from Ca2+-channels, in the impaired exocytotic and secretory responses from palmitate-treated beta-cells, are investigated using mathematical models of Ca2+ dynamics, granule pools, exocytosis and secretion. It is shown that either disruption of Ca2+-channel clusters or dissociation of granules from Ca2+-channels with a shift to a highly calcium-sensitive pool can explain the recent experimental findings of palmitate-induced defects of exocytosis and insulin secretion. On the basis of imaging results, it is argued that a shift to a highly calcium-sensitive state after dissociation of granules from Ca2+-channels is the most likely explanation for the experimental findings from beta-cells exposed chronically to palmitate.}},
author = {{Pedersen, Morten Gram}},
issn = {{0953-8194}},
keywords = {{HCSP; palmitate; insulin secretion; beta-cells; mathematical modelling}},
language = {{eng}},
number = {{12}},
pages = {{1315--1324}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Neuroendocrinology}},
title = {{Insulin Secretory Granules Enter a Highly Calcium-Sensitive State following Palmitate-Induced Dissociation from Calcium Channels: A Theoretical Study}},
url = {{http://dx.doi.org/10.1111/j.1365-2826.2010.02056.x}},
doi = {{10.1111/j.1365-2826.2010.02056.x}},
volume = {{22}},
year = {{2010}},
}