Targets and candidate agents for type 2 diabetes treatment with computational bioinformatics approach.
We sought to explore the molecular mechanism of type 2 diabetes (T2D) and identify potential drug targets and candidate agents for T2D treatment. The differentially expressed genes (DEGs) were assessed between human pancreatic islets with T2D and normal islets. The dysfunctional pathways, the potential transcription factor, and microRNA targets were analyzed by bioinformatics methods. Moreover, a group of bioactive small molecules were identified based on the connectivity map database. The pathways of Eicosanoid Synthesis, TGF-beta signaling pathway, Prostaglandin Synthesis and Regulation, and Integrated Pancreatic Cancer Pathway were found to be significantly dysregulated in the progression of T2D. The genes of ZADH2 (zinc binding alcohol dehydrogenase domain containing 2), BTBD3 (BTB (POZ) domain containing 3), Cul3-based ligases,  LTBP1 (latent-transforming growth factor beta binding protein 1), PDGFRA (alpha-type platelet-derived growth factor receptor), and FST (follistatin) were determined to be significant nodes regulated by potential transcription factors and microRNAs. Besides, two small molecules (sanguinarine and DL-thiorphan) were identified to be capable of reverse T2D. In the present study, a systematic understanding for the mechanism underlying T2D development was provided with biological informatics methods. The significant nodes and bioactive small molecules may be drug targets and candidate agents for T2D treatment.
Department of Endocrinology, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou 450003, China.
Qiong
Q
Wang
Department of Endocrinology, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou 450003, China.
Zhigang
Z
Zhao
Department of Endocrinology, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou 450003, China.
Jing
J
Shang
Department of Endocrinology, Henan Provincial People's Hospital, No. 7 Weiwu Road, Zhengzhou 450003, China.
Wei
W
Xia
D053119:Benzophenanthridines / Q000494:pharmacology; D019295:Computational Biology; D017076:Computer-Aided Design; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D015244:Thiorphan / Q000494:pharmacology
D053119:Benzophenanthridines; D007004:Hypoglycemic Agents; D007546:Isoquinolines; C005705:sanguinarine; D015244:Thiorphan