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EGCG-derived polymeric oxidation products enhance insulin sensitivity in db/db mice 1 1 Introduction 1 2 Results 3 2.1 Preparation and therapeutic effect of EAOP 3 2.2 The therapeutic effect of high-dose E16 3 2.3 The therapeutic effect of low-dose E64 3 2.4 Influence of E64 on SELENOP and TXNIP 3 2.5 The therapeutic effect of different molecular weight fractions 3 2.6 Influence of EAOP on insulin sensitivity 6 2.7 Effects of EAOP on hepatic and renal functions 7 2.8 Delineation of EAOP influence on RAS in HepG2 cells 7 2.9 Tissue and cell coating of EAOP 8 2.10 Influence of EAOP on cholesterol-induced abnormal RAS 9 2.11 Chemical entities of the >50 kDa fraction 9 3 Discussion 10 4 Conclusion 11 5 Materials and methods 11 5.1 Reagents 11 5.2 Preparation of EGCG autoxidation products 11 5.3 Fractionation of E64 by ultrafiltration centrifugation 12 5.4 Animal treatments 12 5.5 ITT 12 5.6 Sample preparation 12 5.7 Serum biomarkers 12 5.8 Liver biomarkers 12 5.9 ROS and hydroxyl radical detection 12 5.10 Western blot 12 5.11 Cell culture 13 5.12 MALDI-TOF-MS instrumentation analysis 13 5.13 Statistical analysis 13 Funding 13 Author contributions 13 Declaration of competing interest 1

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UND

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nonfiction