ABSTRACT
Objective:To observe the therapeutic effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on insulin resistance, and to investigate the molecular mechanisms in T2DM rats.Methods:The T2DM rats were induced by a high fat and high glucose diet for 10 weeks combined with low-dose streptozocin. Four weeks after infusion of HUC-MSCs via tail vein of the rats, fasting blood glucose, triglycerides, cholesterol were measured. Intraperitoneal glucose tolerance test, intraperitoneal insulin tolerance test and hyperinsulinemic-euglycaemic clamp test were performed to evaluate the islet function and insulin resistance level of rats. The protein expression levels of lipid metabolism signal pathway adenine monophosphate activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC) in liver tissue were detected by western blot.Results:Compared with the T2DM group, HUC-MSCs treatment can significantly reduce fasting blood glucose, triglycerides, total cholesterol levels ( P<0.01), and the values of area under the curve of glucose tolerance and insulin tolerance ( P<0.05) in the T2DM+ HUC-MSCs group. Hyperinsulinemic-euglycaemic clamp test found that compared with the T2DM group, after HUC-MSCs treatment, the glucose infusion rate level was significantly higher in the T2DM+ HUC-MSCs group( P<0.01); Western blot showed that compared with the T2DM group, the ratio of p-AMPK to AMPK and p-ACC to ACC in liver tissues of T2DM+ HUC-MSCs group were significantly increased( P<0.01). Conclusion:Human umbilical cord mesenchymal stem cells treatment may improve lipid metabolism and insulin resistance by activating AMPK/ACC signaling pathways in type 2 diabetic rats.
ABSTRACT
Objective To investigate the effects of vaspin on insulin resistants of 3T3-L1 adipocyte through the insulin receptor substrates (IRS) /phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) /glucose transporter (Glut) signaling pathway.Methods 3T3-L1 cells cultured by palmitic acid (PA) were used to establish insulin resistance models,which were divided into PA group,PA + 100 ng/ml vaspin group,PA+200 ng/ml vaspin group,PA+400 ng/ml vaspin group and PA+400 ng/ml vaspin+wortmannin (PI3K inhibitor) group.Glucose uptake and consumption were assessed by 2-deoxy H3-D-glucose incorporation and glucose oxidase-peroxidase respectively.IRS/PI3K/Akt/Glut signaling pathway was evaluated using reverse transcription polymerase chain reaction and Western blot analysis.Results Compared with PA group,glucose uptake and consumption increased gradually with the increasing of vaspin concentration in other groups (P ＜ 0.05).mRNA levels of IRS-1,Akt and Glut 4 increased gradually as vaspin concentration increasing (P＜0.05),and the ratios of p-IRS-1 to IRS-1,p-Akt to Akt and Glut 4 protein level also showed the same trends (P＜0.05).However,glucose uptake and consumption in PA+400 ng/ml vaspin+wortmannin group were less than that of PA +400 ng/ml vaspin group (P＜0.05).PA+400 ng/ml vaspin+wortmannin group showed lower mRNA and protein phosphorylation levels of IRS-1,Akt and Glut 4 (P＜0.05),and that the ratios of p-IRS-1 to IRS-1,p-Akt to Akt and Glut 4 protein levels decreased (P＜0.05).Conclusions Vaspin can improve the insulin sensitivity of 3T3-L1 adipocyte by activating IRS/PI3K/Akt/Glut signaling pathway.
ABSTRACT
The purpose of this investigation was to evaluate the effect of transforming growth factor-beta (TGF-beta) on the efficacy of Schwann cell (SC) and on the repair of peripheral nerve defect. 50 ng x ml(-1) TGF-beta was shown to promote the proliferation of SC by MTT and flow cytometry (FCM) assay, and NGF synthesis in SC culture media was noted to be of significantly higher concentration by ELISA method (P<0.05). SCs mixed with bovine acellular matrix (BAM), fetal bovine serum and media based on definite ratio were injected into polylactideco-glycolide acid (PLGA)guide. 30 SD rats, each had a man-made sciatic nerve defect 15 mm long, were randomly divided into 3 groups: experiment group (PLGA conduit+SC+TGF-beta), control group(PLGA conduit+SC), and autograft group. After 16 weeks, it was demonstrated that the effect of the test group was not significantly different from that of the autograft group, but it was better than that of the control group by means of electrophysiological test and sciatic nerve function index (SFI). TGF-beta can promote not only the proliferation, but also the NGF synthesis of SC obviously. The use of exogenous TGF-beta in the repair of peripheral nerve defect may produce better curative effect.