To investigate the risk genes associated with pancreatic impairments in order to elucidate the key genes and molecular mechanisms underlying the pathogenesis and progression of Type 2 Diabetes Mellitus (T2DM).
Analysis of pancreatic transcriptomes from T2DM patients and healthy populations (GSE20966 and GSE25724) identified differentially expressed genes (DEGs) via R-based screening, and the protein-protein interaction (PPI) network construction. Furthermore, Mendelian randomization (MR) analysis was employed to investigate the causal relationship with T2DM, and the expression patterns of key candidate genes were validated using RT-qPCR and Western blot.
Integrated PPI network and Mendelian randomization analysis revealed consistently upregulated GABBR1and HK1, while HMGCR, HSD17B12, VLDLR, and WIPI1 were significantly downregulated in T2DM versus controls. In a high-fat diet-induced T2DM mouse model, HMGCR expression was significantly downregulated at both the mRNA and protein levels. These findings indicate that HMGCR may play a critical regulatory role in the pathogenesis of T2DM.
These findings suggest that HMGCR is a potential key regulator involved in pancreatic dysfunction in T2DM and may affect β-cell function.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |