Fatty acids and glucose in high concentration down-regulates ATP synthase beta-subunit protein expression in INS-1 cells.
Författare
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.
Avdelning/ar
Publiceringsår
2007
Språk
Engelska
Sidor
273-278
Publikation/Tidskrift/Serie
Nutritional Neuroscience
Volym
10
Issue
5-6
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Taylor & Francis
Ämne
- Nutrition and Dietetics
Status
Published
Forskningsgrupp
- Appetite Regulation
ISBN/ISSN/Övrigt
- ISSN: 1476-8305