| The recent increase in the prevalence of obesity has been associated with a coincident rise in the prevalence of Type 2 diabetes. The pathophysiological mechanisms that have been proposed to explain this link are the rise in the plasma concentrations of free fatty acids (FFAs). Elevated levels of FFAs can lead to lipotoxicity, and evidence is growing thatβcell function is impaired through lipotoxicity, however, the molecular mechanisms responsible remain unknown. MAPK pathways play an important role in regulating the various stresses-induced apoptosis. P38, one member of MAPKs, can be activated by exogenous and endogenous stress, leading to the apoptosis of pancreaticβcell. Insulin-producing MIN6 cells were treated by palmitate, and DNA fragmentation assay and Detection of chromatin condensation were applied to confirm the palmitate-induced apoptosis of MIN6 cells, the results demonstrated palmitate caused the apoptosis of pancreaticβcell by a time and dose-dependent course. Both min6 cells and primary SD rat islets were treated for 0, 1, 6, 12, 24h in the absence or presence of 0.5mM palmitate, and the activities of P38 were analysed by western blot. The results demonstrated that P38 was activated by palmitate in a time and dose-dependent course. The P38 selective inhibitor SB203580 markedly prevented the palmitate-induced apoptosis of MIN6 cells by using flow cytometry, which demonstrates that palmitate-induced P38 activation participates in pancreaticβcell apoptosis. Both min6 cells and SD rat islets were also treated with 0.5mM palmitate in the absence or presence of SB203580, and the activities of ATF2 and MSK1(transcription factors closely related to apoptosis) of P38 substrates were analysed by western blot. It is revealed that palmitate also markedly induced the activation of ATF2 and MSK1, which were suppressed by inhibiting P38. In conclusion, palmitate-induced P38 activtion participates inβcell apoptosis, possibly by enhancing the activities of ATF2 and MSK1. |
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