Abstract
Loss of pancreatic beta-cells by apoptosis appears to play an important role in the development of insulin deficiency and the onset and/or progression of the diabetes mellitus. To this end, we report that curcumin prevents high glucose (HG) induced oxidative stress and apoptosis in mouse pancreatic beta cells. Moreover, curcumin prevents HG induced increase in expression of CHOP, decrease in PCG-1a and phosphorylation of ERK1/2 (pERK1/2) without any effect on the phosphorylation levels of p38 and JNK. Moreover, similar to curcumin, blockade of pERK1/2 reduced the HG induced apoptosis in pancreatic beta cells. Overexpression of CHOP or siRNA knockdown of PCG-1a counteracted the effect of curcumin on HG induced apoptosis and oxidative stress. These results suggest that curcumin acts through CHOP/PCG-1a and ERK1/2 signaling to block the HG induced oxidative stress and apoptosis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
-
Apoptosis / drug effects*
-
Cell Line, Tumor
-
Curcumin / metabolism
-
Curcumin / pharmacology*
-
Extracellular Signal-Regulated MAP Kinases / metabolism*
-
Glucose / metabolism
-
Glucose / pharmacology*
-
Humans
-
Insulin-Secreting Cells / drug effects*
-
Insulin-Secreting Cells / metabolism
-
Mice
-
Mitogen-Activated Protein Kinase 1 / metabolism
-
Mitogen-Activated Protein Kinase 3 / metabolism
-
Oxidative Stress / drug effects*
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
-
Phosphorylation / drug effects
-
RNA Interference
-
Transcription Factor CHOP / genetics
-
Transcription Factor CHOP / metabolism*
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Ddit3 protein, mouse
-
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
-
Ppargc1a protein, mouse
-
Transcription Factor CHOP
-
Extracellular Signal-Regulated MAP Kinases
-
Mapk1 protein, mouse
-
Mapk3 protein, mouse
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Curcumin
-
Glucose