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13 November 2019 : Animal Research

Gegen Qinlian Decoction Ameliorates Hepatic Insulin Resistance by Silent Information Regulator1 (SIRT1)-Dependent Deacetylation of Forkhead Box O1 (FOXO1)

Miao Sui12BDEF, Guofang Chen3CD, Xiaodong Mao3DF, Xiao Wei3CE, Yu Chen3BF, Chao Liu3AE*, Yaofu Fan3ACG

DOI: 10.12659/MSM.919498

Med Sci Monit 2019; 25:8544-8553

Abstract

BACKGROUND: Gegen qinlian decoction (GGQLD) is a form of traditional Chinese medicine used for hundreds of years for its efficacy in treating diabetes. However, the mechanisms underlying the therapeutic effects of GGQLD on diabetes are still not clear. We aimed to evaluate the effect of GGQLD on hepatic insulin resistance (IR) through silent information regulator1 (SIRT1)/forkhead box O1 (FOXO1) in an IR mouse model.

MATERIAL AND METHODS: A high-fat diet (HFD) mouse model was established and GGQLD was administrated by oral gavage. Metabolic parameters were detected, including body weights, triglyceride, fasting glucose, fasting insulin and HOMA-IR index, glucose intolerance, and insulin resistance. HE-stained sections were used to observe the histopathology of liver tissue. For in vitro study, GGQLD-medicated serum was used to treat palmitic acid-stimulated HepG2 cells. The glycogen synthesis and downstream SIRT1/FOXO1 signaling pathways were examined. Specific siRNAs were used to knock down SIRT1 in HepG2 cells.

RESULTS: GGQLD administration significantly decreased body weights, triglyceride level, fasting glucose level, fasting insulin level, and HOMA-IR index, and improved IR in HFD mice. GGQLD enhanced SIRT1 expression and suppressed the expression of Ac-FOXO1 in liver tissues. Further, GGQLD-medicated serum promoted SIRT1 upregulation and suppressed Ac-FOXO1 levels in palmitate-stimulated HepG2 cells. GGQLD-medicated serum also increased the protein expression of PPARĪ³ and reduced the expression of FABP4 in palmitate-stimulated HepG2 cells.

CONCLUSIONS: We found that GGQLD alleviates insulin resistance through SIRT1-dependent deacetylation of FOXO1.

Keywords: Diabetes Mellitus, Forkhead Transcription Factors, Insulin Resistance, sirtuin 1

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750