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Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells.

Köhnke, Rickard LU ; Mei, Jie LU ; Park, Miejung; York, David A and Erlanson-Albertsson, Charlotte LU (2007) In Nutritional Neuroscience 10(5-6). p.273-278
Abstract
Chronic hyperglycemia and hyperlipidemia exert deleterious effects on beta-cell function and impair glucose-induced insulin release, referred to as glucotoxicity and lipotoxticity. These abnormalities are associated with decreased glucose-induced ATP production; ATP serves as an important signal for insulin secretion. To investigate the mechanism of the impaired ATP formation, we examined the effects of elevated glucose and fatty acids levels on ATP synthase beta-subunit expression, ATP content and insulin secretion in INS-1 insulinoma beta-cells. ATP synthase beta-subunit expression was measured by western blot, ATP content was monitored by ATP luminescence and insulin secretion detected by radio immunoassay. Our result indicated that... (More)
Chronic hyperglycemia and hyperlipidemia exert deleterious effects on beta-cell function and impair glucose-induced insulin release, referred to as glucotoxicity and lipotoxticity. These abnormalities are associated with decreased glucose-induced ATP production; ATP serves as an important signal for insulin secretion. To investigate the mechanism of the impaired ATP formation, we examined the effects of elevated glucose and fatty acids levels on ATP synthase beta-subunit expression, ATP content and insulin secretion in INS-1 insulinoma beta-cells. ATP synthase beta-subunit expression was measured by western blot, ATP content was monitored by ATP luminescence and insulin secretion detected by radio immunoassay. Our result indicated that chronic exposure to high doses of fatty acids together with high levels glucose produced a marked decrease in ATP synthase beta-subunit protein expression. Reduction of ATP synthase beta-subunit protein expression occurred with a decreased intracellular ATP concentration and insulin secretion at high fatty acid concentrations. These results indicate that high glucose together with fatty acids impair the production of ATP in beta-cells through the suppression of mitochondrial ATP synthesis. We conclude that ATP synthase beta-subunit may have an important role in the glucolipotoxicity of islet cells and suggest that ATP synthase beta-subunit might be a target of lipotoxicity in beta-cells. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nutritional Neuroscience
volume
10
issue
5-6
pages
273 - 278
publisher
Taylor & Francis
external identifiers
  • pmid:18284036
  • wos:000252714900010
  • scopus:37849046731
ISSN
1476-8305
DOI
10.1080/10284150701745910
language
English
LU publication?
yes
id
f8d1a3e6-0f01-489b-84df-921273c32951 (old id 1041750)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18284036?dopt=Abstract
date added to LUP
2008-03-06 12:01:17
date last changed
2017-09-03 04:50:30
@article{f8d1a3e6-0f01-489b-84df-921273c32951,
  abstract     = {Chronic hyperglycemia and hyperlipidemia exert deleterious effects on beta-cell function and impair glucose-induced insulin release, referred to as glucotoxicity and lipotoxticity. These abnormalities are associated with decreased glucose-induced ATP production; ATP serves as an important signal for insulin secretion. To investigate the mechanism of the impaired ATP formation, we examined the effects of elevated glucose and fatty acids levels on ATP synthase beta-subunit expression, ATP content and insulin secretion in INS-1 insulinoma beta-cells. ATP synthase beta-subunit expression was measured by western blot, ATP content was monitored by ATP luminescence and insulin secretion detected by radio immunoassay. Our result indicated that chronic exposure to high doses of fatty acids together with high levels glucose produced a marked decrease in ATP synthase beta-subunit protein expression. Reduction of ATP synthase beta-subunit protein expression occurred with a decreased intracellular ATP concentration and insulin secretion at high fatty acid concentrations. These results indicate that high glucose together with fatty acids impair the production of ATP in beta-cells through the suppression of mitochondrial ATP synthesis. We conclude that ATP synthase beta-subunit may have an important role in the glucolipotoxicity of islet cells and suggest that ATP synthase beta-subunit might be a target of lipotoxicity in beta-cells.},
  author       = {Köhnke, Rickard and Mei, Jie and Park, Miejung and York, David A and Erlanson-Albertsson, Charlotte},
  issn         = {1476-8305},
  language     = {eng},
  number       = {5-6},
  pages        = {273--278},
  publisher    = {Taylor & Francis},
  series       = {Nutritional Neuroscience},
  title        = {Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells.},
  url          = {http://dx.doi.org/10.1080/10284150701745910},
  volume       = {10},
  year         = {2007},
}