Early Changes Of Insulin Receptor,Insulin Receptor Substrate-1 And Their Tyrosine Phosphorylation In Pancreatic Islets, Liver, Muscle And Adipose Tissue Of High Fat-fed Rats

Objective:(1)To examine dynamically the levels and phosphorylation state of insulin receptor and IRS-1 in pancreatic islets, liver,muscle and adipose tissue in high fat-fed rats compared with normal Wistar rats over 12 weeks until insulin resistance was fully developed. (2)To explore the Chronological and Tissue differences in pancreatic islets and peripheral tissues.Methods:Rat IR model was established with high-fat diet. Setting 6 stages as 1,2,4,6,8,12 week during evolution of IR. Insulin receptor and IRS-1 protein were examined by western blotting, and tyrosine phosphorylation under insulin stimulation by western blotting and immunoprecipitation in pancreatic islets, liver,muscle and adipose tissue.Results:(1) The level of insulin receptor was decreased from the 1st week in liver and pancreatic islets of fat-fed rats compared with normal rats, while it was decreased from the 6th week in muscle and at the 12th week in adipose tissue. The phosphorylation of insulin receptor under insulin stimulation was decreased from the 1st week in liver and muscle, while it was decreased from the 2nd weekin pancreas and adipose tissue. (2) The level of IRS-1 was decreased in the order from the 1st week in liver and the 2nd in pancreatic islet and adipose tissue, while it was decreased from the 4th week in muscle. The phosphorylation of ERS-1 under insulin stimulation was decreased from 1st week in adipose tissue and the 2nd week in liver, while it was decreased until the 12th week in pancreas. And the phosphorylation of IRS-1 was not significant change during the 12 weeks in adipose tissue compared with normal rats. (3) There was an interesting fluctuation that the four proteins above-mentioned were decreased first and restored transiently (entirely or partly) ,then decreased again and remained a low level finally in the four tissues in fat-fed rats during the proceeding of IR.Conclusion rDuring the course of IR development there are chronological differences among tissues. Thus there are chronological and tissue differences in pancreatic islets and peripheral tissues in the evolution of IR.