The Influence Of Tacrolimus On The Function Of Islet Beta Cells

Objective:To investigate the effect of tacrolimus on the insulin secreting function of beta cell and serum GLP-1 concentration in rats. Methods:1、SD rats were treated in different concentration of FK506 by intragastric administration,the concentration of FK506 is divided into group H(2mg/kg·d), group M(1mg/ kg·d),group L(0.5mg/ kg·d),saline as control group(group C),Body weight was measured every three days,fasting for 10 hours a day before gavage,which can drink water during fasting,after gavage for one hour it can take food.2、Before and after intragastric administration of FK506, fasting plasma glucose was measured by glucose oxidase method in every monthly.3、One and four months after FK506 gavage used enzyme linked immunosorbent assay(ELISA) method for the determination of serum fasting insulin.After FK506 gavage for four months to test serum glucagon like peptide-1(GLP-1) level by enzyme linked immunosorbent assay method.4、According to the fasting glucose and fasting insulin calculated the insulin secretion index and insulin resist‘ance index.5、HE staining was used to observe the histological structure changes of islet.6、To compare the different stages and different concentrations of FK506 gavage, the level body mass, FPG, FINS, HOMA-β, HOMA-IR, GLP-1 and pancreatic histological structure changes were observed. Results:1、A month after FK506 gavage, the rats body weight growth value, FPG, FINS, HOMA-beta, HOMA-IR did not change significantly(P>0.05).2、A month after FK506 gavage, pancreatic islet cells of each group had a clear structure, morphology after HE staining.3、Four months after FK506 gavage, the body mass of each group decreased with the increase of FK506 concentration, the H group and M group was significantly lower than that in L, C group(P<0.01), there was no significant difference between L group and C group(P>0.05)4、Four months after the intragastric administration of FK506, FPG of each experimental group are obviously higher than group C, which is most obvious in the H group, blood glucose was positively correlated with FK506 concentration.5、Four months after the intragastric administration of FK506, FPG of each experimental group are obviously higher than group C, which is most obvious in the H group, blood glucose was positively correlated with FK506 concentration.6、 Four months after the intragastric administration of FK506, HOMA-IR levels of each experimental group were increased, and were positively correlated with FK506 concentration.7、After the intragastric administration of FK506 for four months,the expression of GLP-1 of each group were not statistically significant(P>0.05).8、Intragastric administration of FK506 for four months, pancreatic duct of rats in the group H and M had been damaged, the number of islet cells increased, empty gun appeared compared with the C group, histological change of L group was not obvious Conclusion:After intragastric administration with tacrolimus,rat can appear the clinical symptoms of polydipsia and polyuria.Short-term using of tacrolimus will not cause changes of blood glucose and pancreatic beta cell function,later gradually leading to elevated blood sugar, reducing the secretion of insulin, decreasing insulin secretion index, increasing resistance index and pancreatic tissue degeneration,whose changes are related to the concentration of tacrolimus.