Role of MAPK pathway in GPR40 mediated NIT-1 cells lipoapoptosis
AIM: To evaluate the role of MAPK pathway in GPR40 mediated NIT-1 cells lipoapoptosis. METHODS: The effect of silencing GPR40 gene in NIT-1 cells on lipoapoptosis of NIT-1 cells was evaluated and cell apoptosis was detected by Hoechst 33 342, TUNNEL and flow cytometry analysis ( Annexin V/PI). The effects of palmitate, oleate or GPR40 siRNA on MAPK signaling pathway and the effects of PD98059 on oleate-in-hibited lipoapoptosis were also observed. JNK, ERK and p38 ki-nase phosphorylation were detected by Western blot. RESULTS: Palmitate induced β cell apoptosis, which was not mediated through GPR40. The anti-lipoapoptotic activity induced by oleate was suppressed by transfection with GPR40 siRNA. ERK was markedly activated by treatment with oleate. Pretreatment with PD098059 significantly suppressed the anti-lipoapoptotic effect of oleate. Knock-down of GPR40 inhibited the level of ERK1/2 phesphorylation stimulated by oleate. CONCLUSION: Palmitate induces β cell apoptosis by no mediation through GPR40. Oleate protects NIT-1 cells from palmitate-induced lipoapoptosis, partly by mediating through GPR40. The possible mechanism is that ole-ate promotes the activation of ERK MAPK pathway via GPR40, leading to the anti-lipoapaptotic effect on NIT-1 cells.
GTP-binding proltinsmitogen-acfivated protein kinasetype 2 diabetesfree fatty acidsapapto-sisβ cells
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