ABSTRACT
T2DM+LIRA group and T2DM+LIRA+UC-MSCs group (P<0. 05). The ratio of insulin positive area in pancreas tissue was obviously rised, while the ratio of glucagon positive area in pancreas tissue was clearly descended in T2DM+LIRA+UC-MSCs group. And the same difference in valuating islet cells apoptosis by TUNEL could be observed ( P<0. 05). The expression of NF-κB and TLR4 protein in pancreas tissue of T2DM+LIRA+UC-MSCs group were the least amongthefourgroups[(0.75±0.10)vs(0.60±0.08),(0.47±0.08),(0.31±0.04),P<0.05]and[(1.24± 0. 12) vs (0. 93 ± 0. 10), (0. 95 ± 0. 09), (0. 74 ± 0. 07), P<0. 05 ]. Conclusion The combined treatment of liraglutide with umbilical cord mesenchymal stem cells is superior over a single treatment of liraglutide or umbilical cord mesenchymal stem cells in improving the islet function in type 2 diabetes mellitus models, which may be related to the down modulating the TLR4/NF-κB inflammatory signaling pathway.
ABSTRACT
Objective To investigate the effect of liraglutide combined with bone marrow mesenchymal stem cells (BM-MSCs) on glucose metabolism in experimental type 1 diabetic (T1DM) rats.Methods T1 DM rats were established by injecting 60 mg/kg streptozotocin.According to random number table,they were divided into T1DM group (n =10),BM-MSCs group (n =10),LIRA group (n =10),and LIRA+BM-MSCs group (n =10),and were treated for 8 weeks respectively.Random blood glucose,24 h urine volume and protein excretion were tested.Serum concentrations of insulin,C-peptide,glucagon,gastrin,cholecystokinin,and glucagon-like peptid 1 (GLP-1) were assayed by ELISA.Expressions of insulin and glucagon in pancreas were measured by immunohistochemistry.Results After 8 weeks,the levels of random blood glucose,HbA1C,24 h urine volume and 24 h urinary protein excretion in group 4 were significantly decreased compared to the other three groups (P＜0.05).Compared to T1DM group and BM-MSCs group,the levels of insulin,C-peptide,gastrin,cholecystokinin and GLP-1 in LIRA+BM-MSCs group were significantly increased,while glucagon was decreased (P＜0.05).Compared to group LIRA,the levels of insulin,C-peptide,gastrin,and cholecystokinin in LIRA + BM-MSCs group were increased (P ＜ 0.05),there was no significantly difference in glucagon or GLP-1 (P＞0.05).The analysis revealed that the level of insulin was positively correlated with gastrin (r =0.544,P＜0.01),cholecystokinin (r =0.710,P＜0.01) and GLP-1 (r =0.669,P＜ 0.01),but was negatively correlated with glucagon (r =-0.506,P＜0.01);the level of glucagon was negatively correlated with gastrin (r =-0.364,P＜0.05),cholecystokinin (r =-0.433,P＜0.01) and GLP-1 (r =-0.591,P＜ 0.01).Compared to the other three groups respectively,immunohistochemistry displayed that the positive area of insulin in pancreas was significantly increased in LIRA + BM-MSCs group,while that of glucagon was decreased (P＜ 0.05).Conclusions By means of regulating gastrointestinal hormones efficiently,combination of liraglutide withBM-MSCs may improve glucose metabolism more efficaciously than treatment with a single agent in T1DM rats.