Beneficial effects of IH-901 on glucose and lipid metabolisms via activating adenosine monophosphate–activated protein kinase and phosphatidylinositol-3 kinase pathways

Abstract IH-901 is an intestinal metabolite of ginsenosides found in Panax ginseng. In the present study, effects of IH-901 on glucose and lipid metabolisms were examined using C2C12 myotubes and C57BL/ksJ db/db mice. A significant increase in phosphorylated adenosine monophosphate–activated protein kinase was observed when differentiated C2C12 myotubes were treated with IH-901. Glucose transporter 4 protein expressions were also up-regulated when muscle cells were treated with of IH-901 up to 60 minutes, resulting in stimulation of glucose uptake by 25% as compared with untreated cells. In addition, phosphatidylinositol-3 kinase and Akt protein expressions were increased when C2C12 myotubes were exposed to IH-901 for up to 3 hours; and these effects including glucose uptake were attenuated by pretreatment with LY294002, a selective phosphatidylinositol-3 kinase inhibitor. In animal study, IH-901 at 25 mg/kg lowered the plasma glucose, triglyceride, cholesterol, and nonesterified fatty acid levels by 20.7%, 41.6%, 20.2%, and 24.6%, respectively, compared with control mice. In the meantime, plasma insulin levels were significantly increased by 2.2 and 3.4 times in 10 and 25 mg/kg–treated mice, respectively, compared with control mice, in parallel with the histologic observation showing a preserved architecture of the pancreatic islet. Protein and gene expression patterns for adenosine monophosphate–activated protein kinase, sterol regulatory element binding protein–1a, and glucose transporter 4 in the liver and skeletal muscles were similar to those in cell studies. In summary, IH-901 might be a promising therapeutic agent improving altered glucose and lipid metabolisms revealed in type 2 diabetes mellitus patients.