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China Pharmacy ; (12): 1703-1708, 2021.
Artículo en Chino | WPRIM | ID: wpr-882140

RESUMEN

OBJECTIVE:To study the i mprovement effects of α-lipoic acid on glucose metabolism disorder of insulin resistant HepG2 cells. METHODS :The effects of 25-1 000 µmol/L α-lipoic acid on survival rate of human hepatoma cell HepG2 were determined by MTT assay so as to determine the concentration of α-lipoic acid. Negative control group ,insulin resistance group (1× 10-7 mol/L insulin ),combination resistance group (30 µmol/L sodium arsenite+ 1×10-8 mol/L insulin ),α-lipoic acid low- concentration,medium-concentration and high-concentration groups were set up. HepG 2 cells were treated with α-lipoic acid for 12 h and then cultured with corresponding concentration of sodium arsenite or/and insulin for 24 h. The glucose oxidase method was used to detect the glucose consumption ,colorimetric method was used to detect hexokinase activity and pyruvate kinase activity , and anthrone method was used to detect glycogen content. Western blot assay was used to detect the protein expression of GLUT 4, p-GSK3β and GSK3β as well as the ratio of p-Akt/Akt and p-GSK3β/GSK3β. RESULTS:25,50,100 µmol/L α-lipoic acid had no significant effect on the survival rates of HepG 2 cells(P>0.05),and survival rates of H epG2 cells were higher than 96%,so they were used as the low ,medium and high concentration for follow-up study. Compared with negative control group ,glucose consumption,the activities of hexokinase and pyruvate kinase ,glycogen content ,protein expression of GLUT 4 and p-GSK 3β,the ratio of p-Akt/Akt and p-GSK 3β/GSK3β were decreased significantly in insulin resistance group and combined resistance group, while the protein expression of GSK 3β was increased significantly(P<0.05). Compared with combination resistance group ,the glucose consumption (except for α-lipoic acid low- concentration group ),the activities of h exokinase(except for α-lipoic acid low-concentration and medium-concentration groups ) andpyruvate kinase (except for α-lipoic acid low-concentration com and medium-concentration groups ), glycogen contents , protein expression of GLUT 4 (except for α-lipoic acid mail:bliang163@163.com low-concentration group )and p-GSK3β,the ratio of p-Akt/ Akt(except for α-lipoic acid low-concentration and medium-concentration groups )and p-GSK 3β/GSK3β(except for α-lipoic acid low-concentration groups )were increased significantly in α-lipoic acid groups ,while protein expression of GSK 3β(except for α-lipoic acid low-concentration and medium-concentration groups ) was decreased significantly (P<0.05);glycogen content , protein expression of GLUT 4 and the ratio of p-GSK 3β/GSK3β in α-lipoic acid high-concentration group as well as the protein expression of p-GSK 3β in α-lipoic acid medium-concentration and high-concentration groups were improved significantly (P<0.05). CONCLUSIONS:α-lipoic acid can improve the disorder of glucose metabolism in insulin resistant HepG 2 cells,the mechanism of which may be associated with the increase of glucose consumption ,the activities of glucose metabolism related enzymes and glycogen content ,and expression up-regulation of the phosphorylation levels of Akt and GSK 3β protein,the expression of GLUT 4 and p-GSK 3β proteins,down-regulation of the expression of GSK 3β protein.

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