Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo.
OBJECTIVE
Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenoside. We have reported that CK presented anti-diabetic effect via diminishing the expressions of hepatic gluconeogenesis key enzyme. Here, we further explore the possible mechanism of CK on suppression hepatic gluconeogenesis via activation of adenosine-5'monophosphate kinase (AMPK) on type 2 diabetes mice in vivo and in HepG2 cells.


METHODS
Type 2 diabetes mice model was developed by high fat diet combined with STZ injection. 30mg/kg/d CK was orally administrated for 4weeks, the fasting blood glucose level and 2h OGTT were conducted, and the protein expression of AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) were examined. The mechanism of Compound K on hepatic gluconeogenesis was further explored in HepG2 hepatocytes. Glucose production, the protein expression of AMPK, PEPCK, G6pase and PGC-1α, hepatic nuclear factor 4α (HNF-4α) and forkhead transcription factor O1 (FOXO1) were determined after Compound K treatment at the presence of AMPK inhibitor Compound C.


RESULTS
We observed that CK inhibited the expression of PEPCK and G6Pase in the liver and in HepG2 hepatocytes. Meanwhile, CK treatment remarkably increased the activation of AMPK, while decreasing the expressions of PGC-1α, HNF-4α and FOXO1. However, AMPK inhibitor Compound C could reverse these effects of CK on gluconeogenesis in part.


CONCLUSIONS
The results indicated that the effect of CK on suppression hepatic gluconeogenesis might be via the activation the AMPK activity.
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Shengnan
S
Wei
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130018, China.
Wei
W
Li
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Yang
Y
Yu
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Fan
F
Yao
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Lixiang
L
A
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Xiaoxin
X
Lan
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
Fengying
F
Guan
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China. Electronic address: zhangming_00@126.com.
Ming
M
Zhang
Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China. Electronic address: zhouweichen@yahoo.com.
Li
L
Chen
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000627:therapeutic use*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D005894:Panax / Q000737:chemistry; D047492:Peroxisome Proliferator-Activated Receptors
D055372:AMP-Activated Protein Kinases; D036145:Ginsenosides; D005947:Glucose; D005952:Glucose-6-Phosphatase; D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; C112772:ginsenoside compound K
AMP-activated protein kinase; Compound K; Ginseng; Hepatic gluconeogenesis; Type 2 diabetes