Novel role of curcumin in the prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo

Br J Pharmacol. 2008 Nov;155(5):702-13. doi: 10.1038/bjp.2008.311. Epub 2008 Aug 11.


Background and purpose: Oxidative stress caused by cytokine exposure is a major cause of pancreatic islet death in vitro and of diabetogenesis. Antioxidant compounds may prevent cytokine-induced damage to islet cells. Hence, we studied the potential of curcumin, an antioxidant and anti-inflammatory compound, in vitro to protect islets against pro-inflammatory cytokines and in vivo to prevent the progression of diabetes induced by multiple low doses of streptozotocin (MLD-STZ).

Experimental approach: Pancreatic islets from C57/BL6J mice were pretreated with curcumin (10 microM) and then exposed to a combination of cytokines. Islet viability, reactive oxygen species (ROS), NO, inducible NO synthase and NF-kappaB translocation were studied. Curcumin pretreated (7.5 mg kg(-1) day(-1)) C57/BL6J mice were given MLD-STZ (40 mg kg(-1)), and various parameters of diabetes induction and progression were monitored.

Key results: Curcumin protected islets from cytokine-induced islet death in vitro by scavenging ROS and normalized cytokine-induced NF-kappaB translocation by inhibiting phosphorylation of inhibitor of kappa B alpha (IkappaBalpha). In vivo, curcumin also prevented MLD-STZ, as revealed by sustained normoglycaemia, normal glucose clearance and maintained pancreatic GLUT2 levels. Pro-inflammatory cytokine concentrations in the serum and pancreas were raised in STZ-treated animals, but not in animals pretreated with curcumin before STZ.

Conclusions and implications: Here, we have demonstrated for the first time that curcumin in vitro protects pancreatic islets against cytokine-induced death and dysfunction and in vivo prevents STZ-induced diabetes.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal* / therapeutic use
  • Blood Glucose / analysis
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Cytokines / blood
  • Cytokines / pharmacology*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • I-kappa B Proteins / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Reactive Oxygen Species
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Cytokines
  • I-kappa B Proteins
  • Insulin
  • NF-kappa B
  • Nfkbia protein, mouse
  • Reactive Oxygen Species
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Curcumin