Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells.
Author
Summary, in English
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.
Department/s
Publishing year
2007
Language
English
Pages
273-278
Publication/Series
Nutritional Neuroscience
Volume
10
Issue
5-6
Links
Document type
Journal article
Publisher
Taylor & Francis
Topic
- Nutrition and Dietetics
Status
Published
Research group
- Appetite Regulation
ISBN/ISSN/Other
- ISSN: 1476-8305