title: Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells.
abstract: BACKGROUND
  Prolonged elevated levels of lipids have negative effects on beta-cell function and mass (lipotoxicity). To what extent exposure to high glucose concentration is important in the harmful effects of lipids (glucolipotoxicity) has been debated.
  
  
  METHODS
  We addressed beta-cell lipotoxicity by measuring apoptosis in isolated intact control human islets and insulin-secreting cell lines MIN6 and INS-1E cultured in the presence of palmitate and low (5.5 mM) or high (25 mM) glucose for 48 hours.
  
  
  RESULTS
  In both cell lines and human islets palmitate induced apoptosis after culture at low glucose. Palmitate-induced apoptosis was not increased after culture at high compared to low glucose in human islets and MIN6 cells but glucose-induced rise in apoptosis was observed in INS-1E cells. The rise in apoptosis in INS-1E cells was partially reversed by inclusion of AMPK-agonist AICAR. When CPT1-inhibitor etomoxir was included during culture at low glucose palmitate-triggered apoptosis was accentuated both in the islets and the cell lines. Palmitate oxidation in human islets and the cell lines was comparable after culture at low glucose. At high glucose, palmitate oxidation was reduced by 30% in human islets and MIN6 cells but by 80% in INS-1E cells. In INS-1E cells, AICAR increased oxidation of palmitate. Presence of etomoxir at low glucose decreased palmitate oxidation both in the islets and the cell lines.
  
  
  CONCLUSIONS
  In summary, lipotoxicity is evident not only in the presence of high but also low glucose concentrations. Additional effects of glucose are prominent in INS-1E but not in MIN6 cells and intact control human islets, which are able to efficiently oxidize fatty acids at high glucose and in this way avoid glucolipotoxicity.
authors: Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123, Uppsala, Sweden. Ernest.Sargsyan@mcb.uu.se
authors: Ernest
authors: E
authors: Sargsyan
authors: Peter
authors: P
authors: Bergsten
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D046509:Tissue Culture Techniques
chemical_list: D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D010168:Palmitates; D000103:Acetyl-CoA Carboxylase; D005947:Glucose; C054207:etomoxir