Peroxisome proliferator-activated receptor α (PPARα) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism

摘要: Pancreatic beta cells chronically exposed to fatty acids may lose specific functions and even undergo apoptosis. Generally, lipotoxicity is triggered by saturated acids, whereas unsaturated induce lipodysfunction, the latter being characterised elevated basal insulin release impaired glucose responses. The peroxisome proliferator-activated receptor α (PPARα) has been proposed play a protective role in this process, although cellular mechanisms involved are unclear. We modulated PPARα production INS-1E investigated key metabolic pathways genes responsible for metabolism–secretion coupling during culture period of 3 days presence 0.4 mmol/l oleate. In cells, secretory dysfunction primarily induced oleate was aggravated silencing PPARα. Conversely, upregulation preserved glucose-stimulated secretion, essentially increasing response at stimulatory concentration (15 mmol/l), protection we also observed human islets. effect associated with restored oxidation rate anaplerotic enzyme pyruvate carboxylase. overproduction increased both β-oxidation acid storage form neutral triacylglycerol, revealing overall induction lipid metabolism. These observations were substantiated expression levels genes. protected from oleate-induced dysfunction, promoting preservation turnover.