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Tarlliza R Nardelli, Emerielle C Vanzela, Keli C Benedicto, Flora Brozzi, André Fujita, Alessandra K Cardozo, Décio L Eizirik, Antonio C Boschero and Fernanda Ortis

Barthson J Igoillo-Esteve M Grieco FA Villate O Oliveira JM Casimir M , et al . 2015 Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms . Diabetologia 58 2307 – 2316 . ( https

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Huixia Li, Zhuanmin Zhang, Dongxu Feng, Lin Xu, Fang Li, Jiali Liu, Xinxin Jin, Zhuang Qian, Xiaomin Kang and Hongzhi Sun

Progranulin (PGRN), a multifunctional protein implicated in embryonic development and immune response, was recently introduced as a novel marker of chronic inflammation related with insulin resistance in obesity and type 2 diabetes mellitus. However, the potential mechanisms of PGRN on insulin signaling pathways are poorly understood. In this study, PGRN mediated the chemotaxis of RAW264.7, impaired insulin action and stimulated production of inflammatory factors in adipocytes, which was accompanied by increased c-Jun N-terminal kinase (JNK) activation and serine phosphorylation of insulin receptor substrate-1. PGRN knockdown partially led to an increase in insulin action as well as a decrease in the JNK activation and extracellular signal-regulated kinase phosphorylation in cells exposed to tumor-necrosis factor-α (TNF-α). Meanwhile, PGRN treatment resulted in an elevation of transcription factor nuclear factor κB (NF-κB) nuclear translocation and acetylation, and increased Il-1b, Il6, Tnf-a expression, whereas NF-κB inhibition reversed PGRN-induced insulin action impairment and inflammatory gene expression. Finally, we showed that sirtuin 1 (SIRT1) expression was downregulated by PGRN treatment, whereas SIRT1 overexpression improved PGRN-induced insulin resistance, NF-κB activation, and inflammatory gene expression. Our results suggest that PGRN regulates adipose tissue inflammation possibly by controlling the gain of proinflammatory transcription in a SIRT1-NF-κB dependent manner in response to inducers such as fatty acids and endoplasmic reticulum stress.

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S Lortz, S Lenzen and I Mehmeti

Kaufman RJ 2012 Endoplasmic reticulum stress and type 2 diabetes . Annual Review of Biochemistry 81 767 – 793 . ( doi:10.1146/annurev-biochem-072909-095555 ). Bertolotti A Zhang Y Hendershot LM Harding HP Ron D 2000 Dynamic

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Julie Amyot, Isma Benterki, Ghislaine Fontés, Derek K Hagman, Mourad Ferdaoussi, Tracy Teodoro, Allen Volchuk, Érik Joly and Vincent Poitout

HIT cells . Molecular and Cellular Biology 9 1784 – 1789 . Eizirik DL Cardozo AK Cnop M 2008 The role for endoplasmic reticulum stress in diabetes mellitus . Endocrine Reviews 29 42 – 61 . doi:10.1210/er.2007-0015 . Fonseca SG

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Shalinee Dhayal, Francesco P Zummo, Matthew W Anderson, Patricia Thomas, Hannah J Welters, Catherine Arden and Noel G Morgan

-fluorescence LC3 reporter construct. References Abdulkarim B Hernangomez M Igoillo-Esteve M Cunha DA Marselli L Marchetti P Ladriere L Cnop M 2017 Guanabenz sensitizes pancreatic beta cells to lipotoxic endoplasmic reticulum stress

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Bo Zhou, Huixia Li, Jiali Liu, Lin Xu, Qinyue Guo, Hongzhi Sun and Shufang Wu

. For example, mice with a conditional deletion of Atg7 in the intestinal epithelium showed an enhanced mRNA expression of IL1B ( Crisan et al . 2011 ). Additional studies in vivo demonstrated that obesity-induced endoplasmic reticulum stress causes

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Gábor Bánhegyi, Miklós Csala and Angelo Benedetti

3905 – 3915 . Wei Y Wang D Topczewski F Pagliassotti MJ 2006 Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells . American Journal of Physiology 291 E275 – E281 . White PC

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Emily Tubbs and Jennifer Rieusset

obesity . Nature Medicine 20 1427 – 1435 . ( doi:10.1038/nm.3735 ) Ashraf NU Sheikh TA 2015 Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease . Free Radical Research 49 1405

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Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock and Hui Chen

Romero A Stuart RC Nillni EA 2013 Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing . Journal of Biological Chemistry 288 17675 – 17688 . ( doi:10.1074/jbc

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Caitlyn Nguyen-Ngo, Nanthini Jayabalan, Carlos Salomon and Martha Lappas

Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells . PLoS ONE e72344 . ( ) 23977286 Feng H Su R Song Y Wang C Lin LJ Yang H