Journal of Korean Medicine for Obesity Research (한방비만학회지)

The Society of Korean Medicine for obesity Research (한방비만학회)
권호 표지
DOI QR코드

DOI QR Code

The Effects of Galgunhwanggumhwangryun-tang on Glucose and Energy Metabolism in C2C12 Myotubes

C2C12 골격근 세포에서 갈근황금황련탕의 당 대사 및 에너지 조절 효과

  • Jihong, Oh (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Song-Yi, Han (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Soo Kyoung, Lim (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University) ;
  • Hojun, Kim (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Dongguk University)
  • 오지홍 (동국대학교 한의과대학 한방재활의학교실) ;
  • 한송이 (동국대학교 한의과대학 한방재활의학교실) ;
  • 임수경 (동국대학교 한의과대학 한방재활의학교실) ;
  • 김호준 (동국대학교 한의과대학 한방재활의학교실)
  • Received : 2022.10.26
  • Accepted : 2022.11.08
  • Published : 2022.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

Keywords

Acknowledgement

본 연구는 보건복지부 재원으로 '한국보건산업진흥원의 한의학혁신기술개발사업 (HF20C0020)'의 지원을 받아 수행되었으며 이에 감사드립니다. 한편 본 연구의 한약 시료를 제공해주신 한국한의학연구원의 양창섭 박사께 감사드립니다.

References

  1. Petersmann A, Muller-Wieland D, Muller UA, Landgraf R, Nauck M, Freckmann G, et al. Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes. 2019 ; 127(S 01) : S1-S7. https://doi.org/10.1055/a-1018-9078
  2. Sangmo H. Recent perspective of metformin. The Journal of Korean Diabetes. 2021 ; 22 : 85-90. https://doi.org/10.4093/jkd.2021.22.2.85
  3. Kim CH, Han KA, Oh HJ, Tan KE, Sothiratnam R, Tjokroprawiro A, et al. Safety, tolerability, and efficacy of metformin extended-release oral antidiabetic therapy in patients with type 2 diabetes: an observational trial in Asia. J Diabetes. 2012 ; 4(4) : 395-406. https://doi.org/10.1111/j.1753-0407.2012.00220.x
  4. Cho EH, Koh EH, Kim MS, Park JY, Lee KU. Mitochondrial dysfunction and insulin resistance. Korean Diabetes Journal. 2006 ; 30(6) : 409-15.
  5. Montgomery MK, Turner N. Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect. 2015 ; 4(1) : R1-R15. https://doi.org/10.1530/EC-14-0092
  6. Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 2005 ; 115(12) : 3587-93. https://doi.org/10.1172/JCI25151
  7. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017 ; 60(9) : 1577-85. https://doi.org/10.1007/s00125-017-4342-z
  8. Feng J, Wang X, Ye X, Ares I, Lopez-Torres B, Martinez M, et al. Mitochondria as an important target of metformin : The mechanism of action, toxic and side effects, and new therapeutic applications. Pharmacol Res. 2022 ; 177 : 106114.
  9. Tian J, Lian F, Yu X, Cui Y, Zhao T, Cao Y, et al. The efficacy and safety of Chinese herbal decoction in type 2 diabetes : a 5-year retrospective study. Evidence-Based Complementary and Alternative Medicine. 2016 ; 2016 : 5473015.
  10. Li YM, Fan XM, Wang YM, Liang QL, Luo GA. [Therapeutic effects of gegen qinlian decoction and its mechanism of action on type 2 diabetic rats]. Yao Xue Xue Bao. 2013 ; 48(9) : 1415-21. Chinese.
  11. Zhang CH, Xu GL, Liu YH, Rao Y, Yu RY, Zhang ZW, et al. Anti-diabetic activities of Gegen Qinlian Decoction in high-fat diet combined with streptozotocin-induced diabetic rats and in 3T3-L1 adipocytes. Phytomedicine. 2013 ; 20(3-4) : 221-9. https://doi.org/10.1016/j.phymed.2012.11.002
  12. Shin JI, Baek JS, Cho CS. A study on the blood sugar improvement effect and safety of Galgunhwangryunhwanggum-tang for type 2 diabetes without complications : a systemic review and meta-analysis. Korean J Orient Int Med. 2022 ; 43(1) : 22-40.
  13. Ren L, Cheng Y, Qin F. Herbal formula Gegen-Qinlian Decoction for type 2 diabetes mellitus : a meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2020 ; 2020 : 3907920.
  14. Shin NR, Bose S, Wang JH, Ansari A, Lim SK, Chin YW, et al. Flos Lonicera combined with metformin Ameliorates hepatosteatosis and glucose intolerance in association with gut microbiota modulation. Front Microbiol. 2017 ; 8 : 2271.
  15. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 2002 ; 51(10) : 2944-50. https://doi.org/10.2337/diabetes.51.10.2944
  16. Li H, Zhao L, Zhang B, Jiang Y, Wang X, Guo Y, et al. A network pharmacology approach to determine active compounds and action mechanisms of ge-gen-qin-lian decoction for treatment of type 2 diabetes. Evid Based Complement Alternat Med. 2014 ; 2014 : 495840.
  17. Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metabolism. 2009 ; 9(5) : 407-16.
  18. Koh JH, Kim YW, Seo DY, Sohn TS. Mitochondrial TFAM as a signaling regulator between cellular organelles: a perspective on metabolic diseases. Diabetes Metab J. 2021 ; 45(6) : 853-65.
  19. Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A. 2007 ; 104(29) : 12017-22. https://doi.org/10.1073/pnas.0705070104