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

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

Author information

1
Tissue Engineering and Banking Laboratory, National Centre for Cell Science, Pune, Maharashtra, India.

Abstract

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.

PMID:
18695642
PMCID:
PMC2584917
DOI:
10.1038/bjp.2008.311
[Indexed for MEDLINE]
Free PMC Article

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