The Influence Of Metformin To Plasma SFRP5 And Skeletal Muscle Atrophy In Diabetic Rats

Objective:Five weeks after modeling T2DM rats with IR which were then cured with metformin,the followings are studied:(a)to observe the change of concentration of plasma SFRP5 and the change of expression of p-JNK in liver,and observe the the influence of metformin to the regulatory pathway of SFRP5-JNK1;(b)to discuss the influence of metformin to skeletal myopathy via the observation of the change of the rats’ skeletal muscle pathology and the expression of Murf-1,MAFbx-1/Atrogin-1.Methods:45 rats were normally fed for a single week and divided into Normal Control Group(NC Group,n=15)and Diabetes Mellitus Group(DM Group,n=30)according to random number table.DM Group were applied intraperitoneal injection with 2%STZ mixed with buffer solution of citric acid(pH=4.5,30mg/kg).The injections were applied once a day,five days in line.Blood glucose was examined randomly in Day 3 and Day 14,the concentration of blood glucose over 16.7mmol/L means the success of modeling.NC Group were applied the intraperitoneal injection with citric acid(pH=4.5).Successfully modeled DM rats were divided into DM Group(n=15)and Metformin Group(MET Group,n=15).The rats in MET Group were applied gavage administration with metformin 200mg · kg-1 · d-1 while the rats in NC Group and DM Group were applied gavage with water.Each group was synchronized fed,blood glucose and weight were examined once each week.Five weeks after intervene to the successfully modeled rats and 12 hours’ fasting,external jugular vein was picked after chloral hydrate anesthesia and was kept at-80 ℃ for the examination of related biochemical criterion and plasma SFRP5.The changes of the liver and skeletal muscle were examed with HE stain.Immunohistochemical method was used to exam the expression of p-JNK in liver.RT-PCR was used to examed the change of expression of MuRF-1,MAFbx-1/Atrogin-1 in skeletal muscle.Results:(a)Several times of continuous intraperitoneal injection of small doses of STZ successfully copied the model of DM rats,the rise of blood glucose can be seen after 3 days’ injection of STZ,the disorder of glucose and lipid metabolism were appeared five weeks after the success of modeling,FINS were increased significantly;(b)metformin can increase the concentration of SFRP5 in plasma(p<0.05),decrease the expression of p-JNK in liver(p<0.05),and improve the insulin resistance;(c)metformin can slow the progress of atrophy in skeletal muscle of DM rats,and restrain the expression of MAFbx/Atrogin-1(p<0.01).Conclusion:(a)Several times of continuous intraperitoneal injection of small doses of STZ successfully copied the model of DM rats,which trends to T2DM;(b)metformin can increase the concentration of SFRP5 in plasma,decrease the expression in p-JNK of liver,improve the insulin resistance;the regulatory pathway of SFRP5-JNK1 could be the new treatment of diabetes care;(c)metformin can slow diabetes progress in skeletal muscle atrophy via inhibition of ubiquitin proteasome system.