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

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 μ M ) and then exposed to a combination of cytokines. Islet viability, reactive oxygen species (ROS), NO, inducible NO synthase and NF‐κB 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‐κB translocation by inhibiting phosphorylation of inhibitor of kappa B alpha (IκBα). 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. British Journal of Pharmacology (2008) 155 , 702–713; doi: 10.1038/bjp.2008.311 ; published online 11 August 2008