Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways

Abstract

Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

Curcumin and dietary polyphenol research: beyond drug discovery

“…Importantly, a recent clinical trial demonstrated that curcumin intervention in pre-diabetic human subjects lowered the number of individuals who eventually progressed to T2D [18] . Numerous in vitro investigations [17,[20][21][22][23][24][25][26] . For example, Pan et al investigated the protective effects of the curcumin derivative C66 on diabetic cardiomyopathy.…”

“…We found that this shortterm curcumin treatment effectively ameliorated muscular oxidative stress by activation of the anti-oxidative Nrf2 signaling cascade [27] . A recent study by Hao et al demonstrated that in the mouse pancreatic MIN6 β-cell line, curcumin attenuated palmitate-induced cell death, possibly via the activation of cell survival Akt signaling and the inhibition of nuclear translocation of FoxO1 [26] .…”

Curcumin Ameliorates Furazolidone Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells via Inhibiting ROS Production and Mitochondrial Pathway

“…Bcl-2 is one of antiapoptotic Bcl-2 family proteins, which regulates the mitochondrial pathway [33]. Several studies showed that curcumin can block the oxidative stress mediated apoptosis via suppressing the mitochondria apoptotic pathway against cisplatin, palmitate and 6-hydroxydopamin induced cytotoxicity [47][48][49]. These data indicated that curcumin protected L02 cells against FZD induced apoptosis via inhibiting mitochondrial pathway.…”

Oxidative Stress: a Promising Target for Chemoprevention

“…In lung cancer, curcumin induces apoptosis accompanied by changes in intracellular oxidative stress-related enzymes and also by phosphorylation and activation of the mitogen-activated protein kinase signaling pathway factors c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase (Yao et al 2015). In pancreatic B cells, curcumin attenuates palmitate-induced apoptosis through PI3K/AKT/Fox01 and mitochondrial survival pathways (Hao et al 2015). A decrease in ROS with a concomitant increase in various antioxidant and DNA repair genes, such as BRCA-1, H2AFX, and PARP-1, were observed after curcumin treatment (Jain et al 2015).…”