Beneficial effects of IH-901 on glucose and lipid metabolisms via activating adenosine monophosphate-activated protein kinase and phosphatidylinositol-3 kinase pathways.
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.
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Hai-Dan
HD
Yuan
Sung Jip
SJ
Kim
Sung-Hyun
SH
Chung
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012502:Sapogenins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000032:analysis
C482402:20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol; C497387:SREBF1 protein, human; D012502:Sapogenins; D051780:Sterol Regulatory Element Binding Protein 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose