AIM: To investigate the effect of high glucose toxicity on JNK pathway and cell function of INS-1 cells.METHODS: Cultured INS-1 cells with or without IGF-1 exposure, were treated with glucose at 3 concentrations (5.6 mmol/L, 11.2 mmol/L and 33.3mmol/L), respectively. MTT was used to measure the cell viability. Apoptosis was determined by immuno-fluorescence and flow-cytometry analysis. The serine 270 phosphorylation of IRS and phosphorylation of JNK in INS-1 cells were detected in the presence or absence of SP600125 treatment.RESULTS: The cell viability decreased and apoptosis increased with elevated glucose concentrations. The percentage of apoptosis cells was 11.3% in 5.6 G group, 12.7% in 11.2 G group and 28.2% in 33.3 G group. There was remarkable increase in apoptosis in 33.3 G group with a 2.49-fold increase to the cells in the basal 5.6 mmol/L glucose. High glucose activated the serine 270 phosphorylation of IRS correlates with JNK phosphorylation in INS-1 cells. Using Western blotting analysis, the levels of JNK phosphorylation were 3.33 fold increased and serine 270 phosphorylation of IRS was 1.17 fold increased in 33.3 G group compared to 11.2 G group (P<0.01). IGF-1 treatment inhibited phosphorylation of JNK and IRS. SP600125 treatment completely blocked JNK phosphorylation in 11.2 G group and reduced JNK phosphorylation by 90% in 33.3 G group. In addition, SP600125 treatment partly reduced serine 270 phosphorylation of IRS by 88.3% in 11.2 G group and 80% in 33.3 G group, the viability of INS-1 cells increased and the apoptosis decreased.CONCLUSION: The toxicity of chronic high glucose, which inhibits the cells viability and induces the cell apoptosis, might be related to suppress IRS signal by activating the JNK pathway. Blocking the JNK pathway might relieve the effect of glucose toxicity to the β cell function by improving the IRS signal pathway.

AIM:To investigate the effect of high glucose toxicity on JNK pathway and cell function of INS-1 cells.METHODS: Cultured INS-1 cells with or without IGF-1 exposure,were treated with glucose at 3 concentrations (5.6 mmol/L,11.2 mmol/L and 33.3mmol/L),respectively. MTT was used to measure the cell viability. Apoptosis was determined by immuno-fluorescence and flow-cytometry analysis. The serine 270 phosphorylation of IRS and phosphorylation of JNK in INS-1 cells were detected in the presence or absence of SP600125 treatment.RESULTS: The cell viability decreased and apoptosis increased with elevated glucose concentrations. The percentage of apoptosis cells was 11.3% in 5.6 G group,12.7% in 11.2 G group and 28.2% in 33.3 G group. There was remarkable increase in apoptosis in 33.3 G group with a 2.49-fold increase to the cells in the basal 5.6 mmol/L glucose. High glucose activated the serine 270 phosphorylation of IRS correlates with JNK phosphorylation in INS-1 cells. Using Western blotting analysis,the levels of JNK phosphorylation were 3.33 fold increased and serine 270 phosphorylation of IRS was 1.17 fold increased in 33.3 G group compared to 11.2 G group (P

Purpose The clinical advantages of ~(131)I SPECT/CT fusion imaging over planar imaging of differentiated thyroid cancer(DTC) were studied. Materials and Methods 97 DTC accepting ~(131)I therapy after thyroid surgery underwent planar ~(131)I whole-body scan(WBS) and SPECT/CT fusion imaging. The diagnostic performance of ~(131)I-WBS and SPECT/CT were comparatively analyzed. Results The patients had totally 251~(131)I-WBS and 102 SPECT/CT imaging. In comparison to WBS, SPECT/CT fusion images were proven of a few advantages, such as: (1)Fused and 3D images being obtained by SPECT/CT;(2)finding more focus;(3)correctly confirming the position of lesions;(4)locating some ~(131)I negative lesions;and (5)distinguishing physiological or polluted activity. Conclusion ~(131)I SPECT/CT fusion imaging could clearly reveal the shape、sizes、biological status and relation to surrounding tissues, thus providing additional information to ~(131)I-WBS in DTC.

The expression of musclin gene in skeletal muscle of rats fed with high-fat diet and its correlation to insulin resistance.diabetes mellitus and GLUT4 were explored.The results showed that musclin expressin was up-regulated(1.39±0.36 vs 0.31±0.07,P<0.01)in skeletal muscle of rats fed with high-fat diet, suggesting that this finding may be related with insulin resistance and involvement of GLUT-4 expression(1.27 4± 0.32 vs 1.84±0.24.P<0.01).

To investigate the impact of exercise on the expression of adiponectin and GLUT4 mR NA in type 2 diabetic rats, type 2 diabetic rat model was made. The diabetic rats were treated with swimming training for 8 weeks. The expression of adiponectin mRNA in perirenal fat and GLUT4mRNA in skeletal muscles were assessed by reverse transcription polymerase chain reaction (RT PCR) and the levels of blood glucose, serum insulin, and blood lipid were measured. Our results showed that the expression of adiponectin mRNA and GLUT4 mRNA in diabetic model group was decreased by 45 % (P＜0.01), 43 % (P＜0.01) respectively. The gene expression of adiponectin and GLUT4 was increased significantly in swimming group (P＜0.05 and P＜0.01, respectively).Compared with the model group, fasting insulin, TG, TC and FFA were decreased significantly in the training group (P＜0.05 or P＜0.01) as compared with model group. It is concluded that exercise can promote the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats,which may be one of the mechanisms responsible for the amelioration of insulin resistance in the rats.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.