The Intervention Effect And Mechanism Of Thioredoxin-Mimetic Peptide(TXM-CB3)on Type 1 Diabetes

N-acetyl-Cys-Pro-Cys-amide(TXM-CB3),as a member of the thioredoxin mimetic peptide family,can simulate the activity of thioredoxin in vivo and in vitro,and play a crucial role in scavenging free radicals and reducing the accumulation of inflammation.Previous studies have shown that TXM-CB3 has the potential to treat complications of type 2 diabetes,but the relationship between TXM-CB3 and type 1 diabetes remains unknown.Therefore,type 1 diabetes(T1D)mouse model was induced by streptozotocin injection of multiple low-dose and used to explore the intervention and mechanism of TXM-CB3 on T1 D.C57BL/6J mice were divided into normal control group,diabetes model group and diabetes administration group.TXM-CB3(5 mg / kg BW / day and 15 mg / kg BW / day,respectively)was injected intraperitoneally to mice in the administration group for 4 weeks.At last,the effects of TXM-CB3 on glucose and lipid metabolism in type 1 diabetic mice were explored.The main results are as follows:Compared with the diabetes model group,TXM-CB3 reduced blood glucose and improved glucose tolerance in type 1 diabetic mice.ELISA kit detected serum insulin in mice and found that the content was significantly increased.After the mice were sacrificed,pancreas sections were subjected to immunohistochemical studies.The scanning analysis of HE,insulin and glucagon fluorescence double staining revealed that the morphology of pancreatic islets of the mice in the administration group were optimized,insulin secretion increased and glucagon content decreased.The results of liver glycogen detection and real-time quantitative PCR showed that TXM-CB3 can promote liver glycogen synthesis and inhibit the expression of hepatic gluconeogenesisrelated genes PEPCK and G6 Pase in diabetic mice.At the same time,TXM-CB3 administration at a certain dose reduced the content of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C),increased the high density lipoprotein cholesterol(HDL-C)content,and improved blood lipid levels.In addition,TXM-CB3 administration exhibited potent anti-inflammatory activity in the pancreas of diabetic mice,as evidenced by decreased gene expression of TNF-α,MCP1,IL-6,IL-1β and i NOS but increased gene expression of IL-4 and IL-10.Furthermore,TXM-CB3 administration also exhibited potent anti-oxidative activity,as evidenced by reduced pancreatic and serum MDA levels,increased pancreatic GSH content and total antioxidant capacity in serum.In short,TXM-CB3 showed anti-oxidant and anti-inflammatory effects in type 1 diabetic mice,which can improve islet function,promote insulin secretion,and improve blood lipid levels,thereby achieving the effect of reducing blood glucose and treating diabetes.