Emodin And Rhein Stimulate Glucose Uptake Through Activation Of PPARγ

Objective To research the traditional Chinese medicine emodin and rhein which may activate peroxisome proliferator-activated receptor gamma (PPARγ) and improve the glucose uptake by HepG2 hepatocyte, 3T3-L1 adipocytes and C2-C12 cell.Methods 1. The induction of 3T3-L1 adipocytes, C2-C12 cell and culture of HepG2 hepatocyte. 2. Three kinds of cells were treated with emodin and rhein, and the PPARγ and glucose transport protein ( GLUT ) proteins expression levels were evaluated by Western blot analysis. 3. The glucose uptake rates were measured by using 2-deoxy-[~3H]-D-glucose in these cells after treatment with emodin and rhein.Results 1. Both PPARγ and GLUT-2 proteins were increased by emodin dose and time-dependently by HepG2 cell. The highest effects of PPARγ proteins were observed at 90 μmol/L after treatment for 24-h, they were 3.1-to 3.8-fold (P<0.01) of the control. And GLUT-2 proteins reach the highest level at 90 μmol/L after treatment for 16-h, was 2.5- to 4.3-fold ( P<0.01) of the control. The glucose uptake rate in HepG2 cells treated with 90 μmol/L of emodin for 24 h was about 5-fold of control (P<0.01). 2. PPARγ and GLUT-2 proteins were increased by rhein at dose- and time-dependent by HepG2 cell. The highest effects of PPARγ proteins were observed at 90 μmol/L after treatment for 16-h, which were 2.8- to 3.3-fold (P<0.01) of the control. And GLUT-2 proteins reach the highest effects at 90 μmol/L after treatment for 24-h, which was 1.6- to 4.7-times (P<0.01) of the control. The glucose uptake rate in HepG2 cells treated with 180 μmol/L of rhein for 24 h was about 5.7- to 6.7- fold (P<0.01) of control. 3. Both PPARγ and GLUT-4 proteins in C2-C12 cell were increased by emodin at dose-and time-dependent manner. The highest effect of PPARγ proteins was observed at 160 μmol/L after treatment for 24 h, they were 2.5-fold of the control (250±29, t=8.829, P<0.01). GLUT-4 protein reached the highest level at 80 μmol/L after treatment for 24 h, it was 3.2- to 3.6-fold (P<0.01 ) of the control. The glucose uptake rate in C2-C12 cells treated with 80 μmol/L of emodin for 24 h was about 4.9-fold [(453.33±47.10) vs (91.67±23.51), t=11.900, P<0.01] of control. 4. Both PPARγ and GLUT-4 proteins were increased by rhein at dose- and time-dependent by C2-C12 cells. The highest effect of PPARγ proteins was observed at 160 μmol/L after treatment for 24-h, which was 1.6-fold (160±16, t=6.495, P<0.01) of the control. And GLUT-4 proteins reach the highest effect at 80 μmol/L after treatment for 24-h, the effect was 1.7- to 2.2-times (P<0.01) of the control. The glucose uptake rate in C2-C12 cells treated with 80 μmol/L of rhein for 24-h was about 4.7- to 5.7- fold (P< 0.01 ) of control. 5. Both PPARγ and GLUT-4 proteins in 3T3-L1 adipocytes were increased by emodin at dose-and time-dependent. The highest effects of PPARγ proteins were observed at 240 μmol/L after treatment for 24-h, they were 3.3-fold of the control (330±15, t=26.558, P<0.01). And GLUT-4 proteins reach the highest effect at 160 μmol/L after treatment forl6-h, the effects was 4.6- to 5.8- times (P<0.01) of the control. The glucose uptake rate in 3T3-L1 adipocytes treated with 160 μmol/L of emodin for 24-h was about 12.4-fold [(352.0±24.22) vs 28.33, t=23.147, P<0.01] of control. 6. PPARγ and GLUT-4 proteins were increased by rhein at dose- and time-dependent by 3T3-L1 adipocytes. The highest effect of PPARγ proteins was observed at 160 μmol/L after treatment for 24-h, which was 2.8-fold ( 280±14, t=22.269, P<0.01 ) of the control. And GLUT-4 proteins reach the highest effect at 160 μmol/L after treatment for 24-h, the effect was 1.7- to 3.3-times (P<0.01) of the control. The glucose uptake rate in 3T3-L1 cells treated with 160 μmol/L of rhein for 24-h was about 9.3- to 16.0- fold (P< 0.01) of control.