An integrated systematic approach for investigating microcurrent electrical nerve stimulation (MENS) efficacy in STZ-induced diabetes mellitus.

Diabetes mellitus (DM) is a major metabolic disorder and an increasing health problem worldwide. Effective non-invasive therapies for DM are still lacking. Here, we have developed Microcurrent electrical nerve stimulation (MENS), a non-invasive therapy, and tested on 46 mice clustered into five groups, such as control, STZ-induced DM, and MENS treatment groups. Experimental results show that MENS treatment is able to improve seven biochemical indexes (e.g., hemoglobin A1c and glucose level). To investigate the mechanisms of MENS treatment on STZ-induced DM, we selected six representative samples to perform microarray experiments for several groups and developed an integrated Hierarchical System Biology Model (HiSBiM) to analyze these omics data. The results indicate that MENS can affect fatty acid metabolism pathways, peroxisome proliferator-activated receptor (PPAR) signaling pathway and cell cycle. Additionally, the DM biochemical indexes and omics data profiles of MENS treatment were found to be consistent. We then compared the therapeutic effects of MENS with anti-diabetic compounds (e.g., quercetin, metformin, and rosiglitazone), using the HiSBiM four-level biological functions and processes of multiple omics data. The results show MENS and these anti-diabetic compounds have similar effect pathways highly correlated to the diabetes processes, such as the PPAR signaling pathway, bile secretion, and insulin signaling pathways. We believe that MENS is an effective and non-invasive therapy for DM and our HiSBiM is an useful method for investigating multiple omics data.