Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro
Source: By:Jianhao Wu, Qinnan Zhang, Yubiao Yang, Chunyue Wang, Xindi Yue, Zhilu Li, Pingping Yan
DOI: https://doi.org/10.30564/jams.v4i2.3094
Abstract:Objective: To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. Method: LO2 hepatocytes was cultured in vitro, hepatocytes were randomly divided into blank control group, 25 mmol/L glucose solution, 27 mmol/L glucose solution, 29 mmol/L glucose solution, 31 mmol/L glucose solution, 33 mmol/L glucose solution, 35 mmol/L glucose solution treatment group, after determining the optimal concentration as 31 mmol/L, use 30 mmol/L metformin solution, and then divided into blank control group, normal hepatocytes + the optimal concentration of glucose solution, normal hepatocytes + metformin solution , normal hepatocytes+. The optimal concentration of glucose solution normal hepatocytes + metformin solution, calculate the number of hepatocytes on cell count plate respectively in the 12 h, 24 h, 48 h, and use the lactic acid kit to determine the lactic acid value of the cell culture medium of normal liver cells + optimal concentration glucose solution and normal liver cells + optimal concentration glucose solution + metformin solution at 12 h, 24 h, and 48 h, respectively. Results: There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the high-glycemic control group compared with that in the high-glycemic control group without metformin. Conclusions: Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this, it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis.
References:[1] Mu Yiming, Ji Linong, et al. Int J Diabetes, 2016,24 (10):871-884. (in Chinese with English abstract) [J]. Chin J Diabetes,2016,24 (10) :871-884. [2] Dang Yongyan, Ye Xiyun, Shen Jie. Journal of East China Normal University, 2010, (5): 143-148. [3] Su Hongwei, Wei Xue, Pan Hailin et al. Blood Lactic Acid Level and Its Influential Factors in Patients with Type 2 Diabetes [J]. Diabetes mellitus, 2015,32 (2) :215-218. [4] NingGuang. Diabetes mellitus in China [J]. Science China (Life Sciences), 2018,48 (8) : 810-811. [5] Lilian Beatriz Aguayo Rojas,Marilia Brito Gomes. Metformin: an old but still the best treatment for type 2 diabetes[J]. Lilian Beatriz Aguayo Rojas;Marilia Brito Gomes,2013,5(1). [6] Zhang Weina, Yu Min, Sun Meiyun et al. Lactic acidosis caused by metformin: a case report [J]. China Rural Medicine 2020,27(01),43-44. [7] Qiu YP. Careful administration of metformin in special population [J]. Shanghai Journal of Traditional Chinese Medicine 08-09 004 Drug Guidelines. [8] Lin Jian, Zhou Zhiguang. Diagnosis, treatment and progress of diabetic lactic acidosis. Journal of Clinical Internal Medicine, 2017, 34:159-161. [9] Richy FF, Sabido-Espin M, Guedes S, et al. Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care, 2014, 37(8) : 2291-2295. [10] Aharaz A, Pottegard A, Henriksen DP, et al. Risk of lactic aci- dosis in type 2 diabetes patients using metformin: A case control study. PloS One, 2018, 13(5) : e0196122. [11] Xianbin Cai,Xi Hu,Bozhi Cai,et al. Metformin suppresses hepatocellular carcinoma cell growth through inductionof cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulationof cyclin D1 in vitro and in vivo[J]. Oncology Reports,2013,30(5). [12] Guo Yali, Lu Shuming, Li Chunyan, Liu Lina. Int J Cirrhosis,2017,39(04):378-382. (in Chinese with English abstract). [13] Almirall J, Briculle M, Gonzalez clemente JM. Metformin- as-sociated lactic acidosis in type 2 diabetes mellitus : incidence and presentation in common elinical practice. Nephrol Dial Transplant , 2008 ,23:2436- 2438. [14] Lu Zuqian. The value of metguanidine antidiabetic drugs in the treatment of type 2 diabetes [J]. Journal of Clinical Therapeutics,2010,8(04):33-38. [15] McAlister FA, Majumdar SR, Eurich DT et al.The effect of specialist care within the first year on subsequent outcomes in 24 232 adults with new-onset diabetes mellitus:population based cohort study [J].Qual Saf Health Care,2007,16 ( 1) : 6 -11. [16] Tao Wenyu, Chen Jiaoli, Li Xiaojin, Xiong Yuxin, Hong Chao, Wang Xiaoling. Journal of Clinical Medicine, 2019,35(14):2220-2224+2229. (in Chinese with English abstract) [17] Li Yanchen, Huang Caibin, Liu Yao, Xia Wenyan, Xu Rong. The role of high mobility group B1 protein in human hepatocyte malignant transformation induced by high glucose microenvironment [J]. Chinese Journal of Diabetes,2019,27(02):137-142. [18] Li Z, Ding Q, Ling LP, et al.Metformin attenuates motility, contraction, and fibrogenic response of hepatic stellate cells in vivo and in vitro by activating amp-activated protein kinase[J].World J Gastroenterol,2018, 24 (7) :819-832.