Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line

Diabetologia. 2007 Feb;50(2):359-69. doi: 10.1007/s00125-006-0462-6. Epub 2006 Dec 7.


Aims/hypothesis: Acute or chronic exposure of beta cells to glucose, palmitic acid or pro-inflammatory cytokines will result in increased production of the p47(phox) component of the NADPH oxidase and subsequent production of reactive oxygen species (ROS).

Methods: Rat pancreatic islets or clonal rat BRIN BD11 beta cells were incubated in the presence of glucose, palmitic acid or pro-inflammatory cytokines for periods between 1 and 24 h. p47(phox) production was determined by western blotting. ROS production was determined by spectrophotometric nitroblue tetrazolium or fluorescence-based hydroethidine assays.

Results: Incubation for 24 h in 0.1 mmol/l palmitic acid or a pro-inflammatory cytokine cocktail increased p47(phox) protein production by 1.5-fold or by 1.75-fold, respectively, in the BRIN BD11 beta cell line. In the presence of 16.7 mmol/l glucose protein production of p47(phox) was increased by 1.7-fold in isolated rat islets after 1 h, while in the presence of 0.1 mmol/l palmitic acid or 5 ng/ml IL-1beta it was increased by 1.4-fold or 1.8-fold, respectively. However, palmitic acid or IL-1beta-dependent production was reduced after 24 h. Islet ROS production was significantly increased after incubation in elevated glucose for 1 h and was completely abolished by addition of diphenylene iodonium, an inhibitor of NADPH oxidase or by the oligonucleotide anti-p47(phox). Addition of 0.1 mmol/l palmitic acid or 5 ng/ml IL-1beta plus 5.6 mmol/l glucose also resulted in a significant increase in islet ROS production after 1 h, which was partially attenuated by diphenylene iodonium or the protein kinase C inhibitor GF109203X. However, ROS production was reduced after 24 h incubation.

Conclusions/interpretation: NADPH oxidase may play a key role in normal beta cell physiology, but under specific conditions may also contribute to beta cell demise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Clone Cells
  • Cytokines / pharmacology*
  • DNA Primers
  • Female
  • Glucose / pharmacology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / enzymology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / enzymology*
  • Kinetics
  • NADPH Oxidases / genetics*
  • NADPH Oxidases / metabolism*
  • Palmitic Acid / pharmacology*
  • Phagocytes / enzymology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species
  • Transfection


  • Cytokines
  • DNA Primers
  • Reactive Oxygen Species
  • Palmitic Acid
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Glucose