Free fatty acids increase PGC-1alpha expression in isolated rat islets

FEBS Lett. 2005 Feb 28;579(6):1446-52. doi: 10.1016/j.febslet.2005.01.046.


PGC-1alpha mRNA and protein are elevated in islets from multiple animal models of diabetes. Overexpression of PGC-1alpha impairs glucose-stimulated insulin secretion (GSIS). However, it is not well known which metabolic events lead to upregulation of PGC-1alpha in the beta-cells under pathophysiological condition. In present study, we have investigated effects of chronic hyperlipidemia and hyperglycemia on PGC-1alpha mRNA expression in isolated rat islets. Isolated rat islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose-dependently increases PGC-1alpha mRNA expression level in isolated islets. FFA also increases PGC-1alpha expression in mouse beta-cell-derived beta TC3 cell line. In contrast, 25 mM glucose decreases expression level of PGC-1alpha. Inhibition of PGC-1alpha by siRNA improves FFA-induced impairment of GSIS in islets. These data suggest that hyperlipidemia and hyperglycemia regulate PGC-1alpha expression in islets differently, and elevated PGC-1alpha by FFA plays an important role in chronic hyperlipidemia-induced beta-cell dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Colforsin / pharmacology
  • Fatty Acids, Nonesterified / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Glucagon / pharmacology
  • Glucagon-Like Peptide 1
  • Glucose / pharmacology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Peptide Fragments / pharmacology
  • Protein Precursors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Wistar
  • Transcription Factors / genetics*


  • Fatty Acids, Nonesterified
  • Peptide Fragments
  • Protein Precursors
  • RNA, Messenger
  • RNA, Small Interfering
  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • Colforsin
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose