It has been long demanded that a better treatment modality for type 2 diabetes mellitus (T2DM) needs to be established, but few suitable regimens have yet been found. We came across the bioactive mushroom extract, SX-fraction (SXF), which appeared to have a hypoglycemic effect. Hence, we investigated if SXF would actually have such an effect, as well as its possible hypoglycemic mechanism. A small-scale clinical study including ten volunteered T2DM patients was conducted. They took a SXF tablet (500 mg) three times a day for 4 weeks, as the fasting blood glucose (FBG) values were measured periodically. The hypoglycemic mechanism of SXF was explored, focusing on the insulin signal transduction (IST) pathway, using skeletal muscle L6 cells in vitro. We found that all 10 patients demonstrated the significant decreases in their FBG levels, from an average of 205 mg/dL to 116 mg/dL, in 4 weeks. This ~42% decline in FBG is remarkable and none of participants presented adverse effects. We then found that the glucose-suppressed IST pathway in L6 cells was significantly activated with SXF. The three key parameters, insulin receptor (IR), insulin receptor substrate 1 (IRS-1), and protein kinase B (Akt), were all highly phosphorylated and activated. Glucose transporter 4 (GLUT4) was subsequently translocated (to the plasma membrane), and glucose uptake resulted in a ~1.9-fold greater than that of glucose-suppressed cells or 21% higher than that of control (vehicle) cells. In conclusion, SXF demonstrates its hypoglycemic effect on T2DM patients, significantly (~42%) lowering their FBG levels in 4 weeks. Such a hypoglycemic mechanism appears to be associated with insulin sensitization through activation of the IST pathway. Thus, SXF could be a natural, safe, and alternative agent for treatment of T2DM patients, improving their diabetic conditions.
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