This study analyzed the effect of miR-19b on the protective effect of Exendin-4 on islet cells in non-obese diabetic (NOD) mice. Twenty-four NOD/LT mice were randomized, according to the random number table, into a control group (4 µg/kg•day), a low-dose group (2 µg/kg•day Exendin-4), a medium-dose group (4 µg/kg•day Exendin-4) and a high-dose group (8 µg/kg•day Exendin-4) (n=6), with miR-19b expression interfered (an interference group) except for the control group. RT-qPCR was used to detect interference results and different doses of Exendin-4 were given for 8 weeks of intervention after the interference. CD4 + and CD8 + cell levels were detected by flow cytometry, IL-2 and IL-10 levels in the peripheral blood by enzyme-linked immunosorbent assay, and the apoptosis rate of islet cells in the pancreatic tissue by TUNEL. After 4 and 8 weeks of Exendin-4 intervention, mice in the high-dose group had lower blood glucose level than the medium-dose group (P<0.05). The medium-dose group had lower CD4 + cell level than the high-dose group (P<0.05), while the medium-dose group had higher CD8 + cell level than the high-dose group (P<0.05). After 8 weeks of intervention, compared with the medium-dose group, the high-dose group had lower IL-2 level (P<0.05), but higher IL-10 level (P<0.05). After 8 weeks of intervention, the medium-dose group had a higher apoptosis rate than the high-dose group (P<0.05). In conclusion, the decrease in miR-19b expression can improve the therapeutic effect of Exendin-4 on NOD, control blood glucose effectively and improve inflammatory response and immune function, as well as reduce islet cell injury. The increase in the dose of Exendin-4 can further improve its therapeutic effect on NOD.

Apoptosis of islet β cells participates in type 1 diabetes. Exendin-4 promotes islet β cell proliferation and inhibits apoptosis. Glucose metabolism related protein-1 (GMRP-1) has the similar effects on islet β cell. Whether the effect of exendin-4 islet β-cells is regulated by GMRP-1 is not clear. GMRP-1 siRNA or pEGFP-C3-GMRP-1 recombinant plasmid was transfected into MIN6 cells and treated with t-BHP in the presence of exendin-4 (0, 50, 100 and 200 nmol/L) followed by analysis of cell proliferation ability by CCK8 assay, apoptosis by flow cytometry, as well as GMRP-1 protein level by Western blot. After transfection of the plasmid with high expression of GMRP-1, the number of MIN6 cells was increased significantly, and the apoptosis rate was reduced (P < 0.05). With increased exendin-4 concentration, the number of cell proliferation was increased gradually with reduced cell apoptosis (P < 0.05). After the expression of GMRP-1 was decreased after GMRP-1 siRNA interference fragment transfection, the number of MIN6 cells was decreased significantly and the apoptosis was elevated (P < 0.05), whereas, exendin-4’s effect on the proliferation of MIN6 cells and inhibition of apoptosis was attenuated. GMRP-1 affects the proliferation and apoptosis of MIN6 cells, and regulates exonin-4-induced MIN6 cell proliferation and apoptosis.

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