The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic OLETF rats

  • Hwang, Yoo-Cheol (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Oh, Da-Hee (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Choi, Moon Chan (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Lee, Sang Yeoul (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Ahn, Kyu-Jeong (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Chung, Ho-Yeon (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine) ;
  • Lim, Sung-Jig (Department of Pathology, Kyung Hee University School of Medicine) ;
  • Chung, Sung Hyun (Department of Pharmacology and Clinical Pharmacy Laboratory, Kyung Hee University College of Pharmacy) ;
  • Jeong, In-Kyung (Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine)
  • Received : 2015.07.09
  • Accepted : 2015.08.23
  • Published : 2018.03.01
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Abstract

Background/Aims: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: Twenty-four-week-old male OLETF rats were assigned to four groups: control (saline), CK 10 mg/kg, CK 25 mg/kg, or metformin 300 mg/kg (positive control); all treatments were administered orally for 12 weeks. Results: Fasting glucose levels of the CK25 group were significantly lower than those of the control group during the 12 weeks. The results of the oral glucose tolerance test showed that both the glucose concentration after glucose loading and the fasting insulin levels of the CK25 group were significantly lower than those of the control. Hepatosteatosis was significantly improved by CK25. CK25 and metformin significantly increased the phosphorylation of hepatic adenosine monophosphate-activated protein kinase (AMPK). CK25 significantly inhibited the expression of sterol regulatory element-binding protein-1c and fatty acid synthase, while upregulating that of peroxisome proliferator-activated receptor-${\alpha}$ and carnitine palmitoyltransferase-1. Conclusions: CK improved glucose intolerance and hepatosteatosis in HFD-fed OLETF rats through AMPK activation, which has dual mode of action that involves decreasing the synthesis of fatty acids and increasing fatty acid oxidation.

Keywords

Acknowledgement

Supported by : Kyung Hee University

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