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Molecular simulation and cell experimental study of fullerol on GLP-1 target of type 2 diabetes mellitus

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Type 2 diabetes mellitus (T2DM) is a complex, progressive disease affecting an estimated 420 million people worldwide. It is responsible for over 90% of people with diabetes. GLP-1 (glucagon-like peptide-1) has a biological function that can help diabetes treatment by increasing insulin production. Bovine Serum Albumin is the main common plasma protein, with a half-life of nineteen days, and when utilized as an agonist, it helps prevent diabetic complications. Fullerenols, on the other hand, have been reported to have antidiabetic efficacy. This work tested fullerenol in vitro on GLP-1, BSA, and MIN6 cells. C60(OH)n effects on GLP-1 and BSA were studied utilizing spectroscopy (fluorescent and UV-Vis’s absorption spectroscopy) and molecular docking techniques. Meanwhile, the antioxidant and ROS scavenging effects of C60(OH)n on hydrogen peroxide-induced oxidative stress in MIN6 cells was investigated using MTT and ROS Assay to understand better C60(OH)n antioxidant and ROS scavenging ability in the H2O2-induced cell. In the ultraviolet-visible spectrum, the combination of GLP-1 and fullerenol has the most significant absorption peak at 276 nm. There was no discernible difference in peak intensity or position relative to GLP-1 maximum absorption peak. The fluorescence experiment used excitation and emission wavelengths of 280 nm and 348 nm, respectively. The C60(OH)n-GLP-1 complex was impacted by changes in fullerenol concentrations, with lower fluorescence spectrum intensities as C60(OH)n concentration increased. The binding constant (Ka) and the binding site were both affected by temperature, according to our findings (n). With increasing temperature, the binding constant (Ka) increased from 4.168 ± 0.252 (L.mol-1) at 273K to 4.183 ± 0.135 (L.mol-1) at 310 K;however, the binding site reduced from 0.864 ± 0.05 at 273K to 0.854 ± 0.03 at 310K. The recorded free energy (G0) was negative, indicating spontaneous exchanges, further confirmed by molecular docking. Dynamic quenching was the effect investigated. GLP-1''s inherent fluorescence was suppressed by fullerenol, according to our findings.

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