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

Kanitkar, M. ; Gokhale, K. ; Galande, S. ; Bhonde, R. R. (2008) Novel role of curcumin in prevention of cytokine-induced islet death in vitro and diabetogenesis in vivo British Journal of Pharmacology, 155 (5). pp. 702-713. ISSN 0007-1188

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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 µM) 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.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Curcumin; Cytokines; Islet Death; MLD-STZ
ID Code:86188
Deposited On:08 Mar 2012 11:15
Last Modified:08 Mar 2012 11:15

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