Cellular Signaling Pathways in Insulin Resistance-Systems Biology Analyses of Microarray Dataset Reveals New Drug Target Gene Signatures of Type 2 Diabetes Mellitus

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis.Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes). The genetic interaction network of both T2DM-associated seeder as well as signature genes generally relates well with the disease condition based on toxicogenomic and data curation.Results: These networks showed significant enrichment of insulin signaling, insulin secretion and other T2DM-related pathways including JAK-STAT, MAPK, TGF, Toll-like receptor, p53 and mTOR, adipocytokine, FOXO, PPAR, P13-AKT, and triglyceride metabolic pathways. We found some enriched pathways that are common in different conditions. We recognized 11-signaling pathways as a connecting link between gene signatures in insulin resistance and T2DM. Notably, in the drug-gene network, the interacting genes showed significant overlap with 13-FDA approved and few non-approved drugs. This study demonstrates the value of systems genetics for identifying 18 potential genes associated with T2DM that are probable drug targets.Conclusions: This integrative and network based approaches for finding variants in genomic data expect to accelerate identification of new drug target molecules for different diseases and can speed up drug discovery outcomes.

Activity of wild Japanese macaques in Yakushima revealed by camera trapping: Patterns with respect to season, daily period and rainfall

“…Our prediction on seasonality was supported; we found that temperature positively affected the activity of Japanese macaques during the studied year, indicating that macaques were more active when the thermal conditions were favorable. The thermoneutral zone, i.e., the ambient temperature range that does not require animals to allocate additional energetic costs to thermoregulation, is reported to be 5–28°C for colobus monkeys [ 49 ], 20–27°C for titis [ 50 ], 25–30 for tarsiers [ 51 ], 25–32°C for sportive lemurs [ 52 ], above 27°C for mouse lemurs [ 53 ], 27–34°C for pygmy marmosets [ 54 ] and 17–28°C for chimpanzees [ 55 ]. Even though the thermoneutral zone for macaques has not been reported, a feeding experiment on captive macaques indicated that they changed food intake and food selection when room temperature decreased from 29 to 15°C [ 56 ].…”

Identification of COL1A1 as an invasion‑related gene in malignant astrocytoma

“…Bioinformatics, including nucleic acid sequence analysis, protein sequence analysis and genomics, can be used to collect, process, store, classify, analyze and interpret biological information through the application of mathematics and computer technology. For example, when combined with microarray technology, bioinformatics analysis can identify the connection between meaningful molecular interactions and evaluate the associated signaling pathways ( 4 ).…”

Variations in ADIPOR1 But Not ADIPOR2 are Associated With Hypertriglyceridemia and Diabetes in an Admixed Latin American Population

“…Insulin resistance has been described as an early stage in the pathogenesis of glucose intolerance and T2DM [59]. Therefore, we assessed a possible relationship between ADIPOR1/2 variations, serum insulin concentrations, and HOMA-IR in the present study.…”