Tacrolimus induces insulin receptor substrate 1 hyperphosphorylation and inhibits mTORc1/S6K1 cascade in HL7702 cells  

作　　者：Hao-Yan Li Yi Wang Min Ran Fei Gao Bo-Yu Zhu Hai-Ying Xiao Chun Xu 

机构地区：[1]Department of Endocrinology,The Third Medical Center of PLA General Hospital,Beijing 100039,China

出　　处：《World Journal of Diabetes》2025年第2期175-182,共8页世界糖尿病杂志(英文)

摘　　要：BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.

关 键 词：TACROLIMUS Insulin resistance DYSLIPIDEMIA Ribosomal protein S6 kinase beta-1 Glucose metabolism 

分 类 号：R58[医药卫生—内分泌]