Mus musculus musculus strain:C57BL/6 Raw sequence reads
This study focused on exploring the effects of SW033291, an inhibitor of 15-hydroxyprostaglandin dehydrogenase, on type 2 diabetes mellitus (T2DM) mice from a comprehensive perspective. Studies have demonstrated that SW033291 benefits tissue repair, organ function, and muscle mass in elderly mice. Our recent investigation initially reported the beneficial role of SW033291 on T2DM progression. Herein, we used a T2DM mouse model induced by a high-fat diet and streptozotocin injection. Then, serum and liver metabolomics as well as liver transcriptomics were performed to provide a systematic perspective of the SW033291-ameliorated T2DM. Results indicated SW033291 improved T2DM by regulating steroid hormone biosynthesis and linoleic/arachidonic acid me-tabolism. Furthermore, integrated transcriptomics and metabolomics analyses suggested that key genes and metabolites such as Cyp2c55, Cyp3a11, Cyp21a1, Myc, Gstm1, Gstm3, and 9,10-dihydroxyoctadecenoic acid, 11-dehydrocorticosterone, and 12,13-dihydroxy-9Z-octadecenoic acid played crucial roles in these pathways. qPCR analysis val-idated the significant decreases in hepatic gene expressions of Cyp2c55, Cyp3a11, Myc, Gstm1, and Gstm3 in the T2DM mice, which were reversed following SW033291 treatment. On the contrary, the elevated mRNA level of Cyp21a1 in T2DM mice was decreased after SW033291 administration. Taken together, our findings suggest SW033291 has promising potential in alleviating T2DM and could be a novel therapeutic candidate.