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

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 PPARγ 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.

• Authors: Miao Sui, Guofang Chen, Xiaodong Mao, Xiao Wei, Yu Chen, Chao Liu, Yaofu Fan
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 8544-8553 (Nov 13 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 31719515 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• FOXO1 protein, human
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Foxo1 protein, mouse
• Insulin
• gegenqinlian
• Palmitic Acid
• SIRT1 protein, human
• Sirt1 protein, mouse
• Sirtuin 1
• Glucose

Topics

• Animals
• China
• Diet, High-Fat
• Disease Models, Animal
• Drugs, Chinese Herbal (metabolism, pharmacology)
• Forkhead Box Protein O1 (genetics, metabolism)
• Forkhead Transcription Factors (metabolism)
• Glucose (metabolism)
• Hep G2 Cells
• Humans
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Liver (metabolism)
• Male
• Medicine, Chinese Traditional (methods)
• Mice
• Mice, Inbred C57BL
• Palmitic Acid (pharmacology)
• Signal Transduction
• Sirtuin 1 (metabolism)