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Insulin Secretory Granules Enter a Highly Calcium-Sensitive State following Palmitate-Induced Dissociation from Calcium Channels: A Theoretical Study

Pedersen, Morten Gram LU (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)
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author
organization
publishing date
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
2011-04-04 10:26:40
date last changed
2018-05-29 10:58:36
@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},
  keyword      = {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},
  volume       = {22},
  year         = {2010},
}