Human umbilical cord mesenchymal stem cells-derived exosomes enhance regulation of hepatic insulin signaling on lipid metabolism through downstream of tyrosine kinase 1 in type 2 diabetic rats
10.13200/j.cnki.cjb.004573
- VernacularTitle:人脐带间充质干细胞外泌体通过酪氨酸激酶下游蛋白1增强2型糖尿病大鼠肝脏胰岛素信号对脂质代谢的调控
- Author:
ZHANG Haocheng
- Publication Type:Journal Article
- Keywords:
Human umbilical cord mesenchymal stem cells-derived exosome(hucMSCs-exo);
Type 2 diabetes mellitus(T2DM);
Lipid metabolism;
Insulin resistance(IR);
Downstream of tyrosine kinase 1(Dok1)
- From:
Chinese Journal of Biologicals
2025;38(10):1194-1202+1210
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which human umbilical cord mesenchymal stem cells-derived exosomes(hucMSCs-exos) improve hepatic insulin resistance(IR) in rats with type 2 diabetes mellitus(T2DM).Methods Male Wistar rats were divided into control, T2DM and hucMSCs-exo groups, with 8 rats in each group. The rats in T2DM group were fed with high-fat diet for 40 days, and then injected with streptozotocin(30 mg/kg) intraperitoneally for modeling. The oral glucose tolerance test(OGTT) was performed 7 days after modeling to verify the model. Treatment regimen: Rats in the control and T2DM groups were injected with 0. 4 mL PBS buffer via the tail vein, and rats in the hucMSCs-exo group were injected with hucMSCs-exo(3 mg/kg, dissolved in 0. 4 mL PBS buffer) via the tail vein for a total of 4 injections at an interval of 1 week. An automatic biochemical analyzer was used to measure the levels of triglyceride(TG), total cholesterol(TC), high density lipoprotein(HDL), low density lipoprotein(LDL) and free fatty acids(FFAs). The pathological changes in the liver were assessed by HE staining. The expression levels of genes and proteins involved in lipid metabolism and insulin signaling,including downstream of tyrosine kinase 1(Dok1), insulin receptor substrate 1/2(Irs1/2), phosphatidylinositol 3-kinase(Pi3k),protein kinase B(Akt) and sterol regulatory element binding protein-1c(Srebp1c) were determined by qPCR and Western blot.Results Compared to the T2DM group, fasting blood glucose was significantly reduced in the hucMSCs-exo group after day 24(day 24: P = 0. 010 9; day 28: P = 0. 005 4). Fasting blood glucose, 90-minute, and 120-minute postprandial glucose levels were significantly reduced after treatment(P = 0. 002 1, 0. 002 9 and < 0. 000 1, respectively). HucMSCs-exo treatment also reduced the levels of LDL and FFAs in T2DM rats(P = 0. 011 3 and 0. 002 5, respectively). The treatment reduced hepatic steatosis in T2DM rats, significantly increased the expression of Dok1 and Akt(each P < 0. 000 1) and reduced the expression of Srebp1c(P = 0. 031 5). The treatment upregulated the expression of DOK1 and p-AKT/AKT(P = 0. 024 1 and <0. 000 1, respectively), and significantly downregulated the expression of SREBPLC(P < 0. 000 1).Conclusion HucMSCsexos reduce hepatic lipid ectopic accumulation by upregulating DOK1, thereby restoring hepatic insulin sensitivity,normalizing hepatic lipid metabolism, and ameliorating the progression of T2DM.
