Scientific article
Open access

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

Published inDiabetologia, vol. 53, no. 2, p. 331-340
  • Open Access - Licence nationale Springer
Publication date2010

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

  • Adenosine Triphosphate/metabolism
  • Antigens, CD36/genetics
  • Apoptosis/drug effects
  • Carbohydrates/ physiology
  • Carnitine O-Palmitoyltransferase/genetics
  • Cell Culture Techniques
  • Fatty Acids, Nonesterified/pharmacology
  • Gene Expression Regulation
  • Glucose/pharmacology
  • Humans
  • Insulin/secretion
  • Insulin-Secreting Cells/cytology/drug effects/pathology/ physiology
  • Oleic Acid/ toxicity
  • PPAR alpha/pharmacology/ physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tubulin/genetics
Citation (ISO format)
FRIGERIO, Francesca et al. Peroxisome proliferator-activated receptor alpha (PPARalpha) protects against oleate-induced INS-1E beta cell dysfunction by preserving carbohydrate metabolism. In: Diabetologia, 2010, vol. 53, n° 2, p. 331–340. doi: 10.1007/s00125-009-1590-6
Main files (1)
Article (Published version)
ISSN of the journal0012-186X

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