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

Abstract

Chronic hyperglycemia and hyperlipidemia exert deleterious effects on β-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 β-subunit expression, ATP content and insulin secretion in INS-1 insulinoma β-cells. ATP synthase β-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 β-subunit protein expression. Reduction of ATP synthase β-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 β-cells through the suppression of mitochondrial ATP synthesis. We conclude that ATP synthase β-subunit may have an important role in the glucolipotoxicity of islet cells and suggest that ATP synthase β-subunit might be a target of lipotoxicity in β-cells.

Keywords:

• ATP SYNTHASE
• ATP CONTENT
• GLUCOSE
• FFA
• INS-1 CELLS