Ruo Lan Xiang1, Mei Mei2, Yun Chao Su1, Li Li1, Jin Yu Wang1, Li Ling Wu1. 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China. 2. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Abstract
OBJECTIVE: Interferon-γ (IFN-γ) plays an important role in apoptosis and was shown to increase the risk of diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatory properties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in rat pancreatic β-cells. METHODS: The RINm5F (rat insulinoma cell line) cells exposed to IFN-γ were treated with or without visfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. The expressions of mRNA and protein were detected by using real-time PCR and western blot analysis. RESULTS: The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of the cells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosis induced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein, decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatin pretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic action of visfatin was attenuated by the AMPK and ERK1/2 inhibitor. CONCLUSION: These results suggested that visfatin protected pancreatic islet cells against IFN-γ-induced apoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin is mediated by activation of AMPK and ERK1/2 signaling molecules.
OBJECTIVE: Interferon-γ (IFN-γ) plays an important role in apoptosis and was shown to increase the risk of diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatory properties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in ratpancreatic β-cells. METHODS: The RINm5F (ratinsulinoma cell line) cells exposed to IFN-γ were treated with or without visfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. The expressions of mRNA and protein were detected by using real-time PCR and western blot analysis. RESULTS: The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of the cells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosis induced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein, decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatin pretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic action of visfatin was attenuated by the AMPK and ERK1/2 inhibitor. CONCLUSION: These results suggested that visfatin protected pancreatic islet cells against IFN-γ-induced apoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin is mediated by activation of AMPK and ERK1/2 signaling molecules.
Authors: Sophie R Sayers; Rebecca L Beavil; Nicholas H F Fine; Guo C Huang; Pratik Choudhary; Kamila J Pacholarz; Perdita E Barran; Sam Butterworth; Charlotte E Mills; J Kennedy Cruickshank; Marta P Silvestre; Sally D Poppitt; Anne-Thea McGill; Gareth G Lavery; David J Hodson; Paul W Caton Journal: Diabetologia Date: 2019-11-15 Impact factor: 10.122