12b-hydroxy-des-D-garcigerin A enhances glucose metabolism in insulin-resistant HepG2 cells via the IRS-1/PI3-K/Akt cell signaling pathway.
HepG2 cells were induced with a high concentration of insulin to establish an insulin-resistant cell model (HepG2/IR). The effect of 12b-hydroxy-des-D-garcigerin A (DGA) on the glucose consumption (GC) of HepG2/IR cells was analyzed with the glucose oxidase/peroxidase assay. The results showed that DGA significantly stimulated GC by enhancing the activity of hexokinase (HK) and pyruvate kinase (PK) in HepG2/IR cells. The cell signaling pathway by which DGA enhances the GC of HepG2/IR cells was explored. The results showed that DGA promoted the expression of insulin receptor (InsR) protein, and stimulated the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3 kinase (p-PI3-K), and phospho-protein kinase B Serine(473) (p-AKT ser(473)). Therefore, we concluded that DGA improved the insulin-resistance of HepG2/IR cells by inducing the IRS-1/PI3-K/Akt cell signaling pathway. Interestingly, DGA had no effect on the phosphorylation of threonine(172) (Thr(172)) in AMP-activated protein kinase (AMPK).
a College of Chemistry and Material Sciences, South-Central University for Nationalities , Wuhan 430074 , China.
Yu
Y
Chen
b College of Pharmacy, South-Central University for Nationalities , Wuhan 430074 , China.
Sha
S
Wang
c College of Life Science, South-Central University for Nationalities , Wuhan 430074 , China.
Shi-Ting
ST
Tian
b College of Pharmacy, South-Central University for Nationalities , Wuhan 430074 , China.
Xin
X
Hu
b College of Pharmacy, South-Central University for Nationalities , Wuhan 430074 , China.
Jing
J
Xu
b College of Pharmacy, South-Central University for Nationalities , Wuhan 430074 , China.
Guang-Zhong
GZ
Yang
c College of Life Science, South-Central University for Nationalities , Wuhan 430074 , China.
Chao-Yuan
CY
Wang
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
C000613641:12b-hydroxy-des-D-garcigerin A; D000935:Antifungal Agents; D055504:Insulin Receptor Substrate Proteins; D044004:Xanthones; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
12b-hydroxy-des-D-garcigerin A; AMP-activated protein kinase; HepG2; IRS-1/PI3-K/Akt cell signaling pathway; glucose consumption; insulin-resistance