Effects of tacrolimus on insulin signal transduction / 中华内分泌外科杂志

ABSTRACT

Objective To observe of the effects of tacrolimus on blood glucose,insulin secretion and the expression of phosphorylated AKT in rats in order to study the mechanism of diabetogenic effects of tacrolimus.Methods 40 male SD rats were randomly divided into two groups.The rats in tacrolimus group were delivered tacrolimus at a dose of 4mg/kg· d.The rats in the control group were given the same amount of saline solution in the same way.The body weights,fasting blood glucose levels and blood concentrations of tacrolimus were measured monthly.After 5 months,all rats were killed.Pancreas and liver tissue were stored in 4％ paraformaldehyde solution.Serum insulin levels were detected by radioimmunoassay method.The expression of phosphorylated AKT in liver were measured by immunohisto-chemical method.Results ①The body weights in tacrolimus group in the 3rd,4th,and 5th month were significantly lower than those in the control group (P＜0.01).②The blood glucose levels in tacrolimus group in the 3rd,4th,and 5th month were significantly higher than those in the control group (P＜0.05).③The insulin secretion and insulin sensitivity index in tacrolimus group were significantly lower than those in the control group (P＜0.01).④The rats in tacrolimus group showed varying degrees of damage in pancreatic duct and pancreatic islet cells.⑤The expression of phosphorylated AKT in liver cells in tacrolimus group were significantly lower than those in the control group (P＜0.05).Conclusions Tacrolimus can induce pancreatic islet cells necrosis,decrease the number of islet cells,reduce insulin secretion and insulin sensitivity,which lead to blood hyperglycemia in rats.In addition,we also find that tacrolimus can reduce expression of phosphorylated AKT in hepatic tissue,which indicates that tacrolimus results insulin resistance through interfering PI3K/ AKT signal transduction pathways.