Protective effects of combining human umbilical cord mesenchymal stem cells and glucagon like peptide-1 receptor agonist on the islet inflammatory injury in rat model of type 2 diabetes mellitus

Abstract

Objective To investigate the effects and mechanism of combining human umbilical cord mesenchymal stem cells and liraglutide on the islet function of type 2 diabetes mellitus SD rats. Method Type 2 diabetes mellitus rats were established by giving high carbonhydrate and fat diet for 4 weeks to SD rats, and then 30 mg/kg streptozotocin was injected intraperitoneally. Type 2 diabetes mellitus rats were randomly divided into four groups according the table of random number: Type 2 diabetes mellitus group(T2DM group), umbilical cord mesenchymal stem cells treatment group(T2DM+ UC-MSCs group), liraglutide treatment group(T2DM+ LIRA group)and liraglutide combined umbilical cord mesenchymal stem cells treatment group(T2DM+ LIRA+ UC-MSCs group). Each group included 10 rats, and rats were given the appropriate drug therapy for 8 weeks. HbA1C, insulin, C-peptide, and glucagon levels were measured. The expressions of insulin and glucagon in pancreas tissue were measured through immunohistochemistry analysis. The apoptosis status of the islet cells in pancreas tissue were evaluated through TUNEL. And the expressions of the nuclear factor-κB(NF-κB)and Toll-like recpter 4(TLR4)protein in pancreas tissue were determined by Western blot. Result After 8 weeks treatment, compared with T2DM group, HbA1C of T2DM+ UC-MSCs group、T2DM+ LIRA group and T2DM+ LIRA+ UC-MSCs group decreased significantly, and it was lowest in T2DM+ LIRA+ UC-MSCs group [(9.1±0.4)% vs (7.2±0.4)%, (3.9±0.3)%, (3.1±0.3)%, respectively, P <0.05]. The insulin and C-peptide of T2DM+ UC-MSC group were significantly increased(P<0.05). The insulin and C-peptide were increased while the glucagon was significantly decreased in 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 among the four groups [(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. (Chin J Endocrinol Metab, 2016, 32: 1003-1009) Key words: Diabetes mellitus, type 2; Liraglutide; Mesenchymal stem cells; Islet function; TLR4/NF-κB pathway