Related Experiment Video
Updated: Mar 8, 2026
Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic
Yoo-Cheol Hwang1, Da-Hee Oh1, Moon Chan Choi1
1Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea.
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-α 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.
Insights
Compound K (CK) effectively treats non-alcoholic fatty liver disease and insulin resistance in diabetic rats. CK activates AMPK, reducing fatty acid synthesis and increasing oxidation for improved liver health.
Area of Science:
- Metabolic disease research
- Pharmacology
- Hepatology
Background:
- Non-alcoholic fatty liver disease (NAFLD) is linked to insulin resistance.
- Compound K (CK), a ginsenoside metabolite, shows potential antidiabetic effects.
- The liver-specific mechanisms and effects of CK on NAFLD are not well understood.
Purpose of the Study:
- To investigate the therapeutic effects of Compound K (CK) on hepatosteatosis.
- To elucidate the underlying molecular mechanisms of CK's action in a high-fat diet (HFD)-induced type 2 diabetes rat model.
Main Methods:
- Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for type 2 diabetes and NAFLD, were used.
- Rats were treated with varying doses of CK (10 mg/kg, 25 mg/kg) or metformin (300 mg/kg) for 12 weeks.
- Key metabolic parameters, glucose tolerance, insulin levels, and gene expression related to lipid metabolism were analyzed.
Main Results:
- Compound K (CK) at 25 mg/kg significantly reduced fasting glucose and improved oral glucose tolerance and insulin sensitivity.
- CK treatment markedly ameliorated hepatosteatosis in HFD-fed rats.
- CK activated hepatic adenosine monophosphate-activated protein kinase (AMPK) and modulated key enzymes involved in fatty acid metabolism.
Conclusions:
- Compound K (CK) improves glucose intolerance and hepatosteatosis in a preclinical model of type 2 diabetes and NAFLD.
- CK's beneficial effects are mediated through the activation of the AMPK pathway.
- This activation leads to a dual mechanism of reduced fatty acid synthesis and enhanced fatty acid oxidation in the liver.
Related Concept Videos
01:25cAMP-dependent Protein Kinase Pathways
01:23Dipeptidyl Peptidase 4 Inhibitors
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:16Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...