The Journal of biological chemistry, 2019-07, Vol.294 (27), p.10415-10427
2019
Details
- Autor(en) / Beteiligte
- Titel
- The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake
- Ist Teil von
- The Journal of biological chemistry, 2019-07, Vol.294 (27), p.10415-10427
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Hypoglycemic drugs such as metformin increase glucose uptake and utilization by peripheral tissues to maintain glucose homeostasis, and the AMP-activated protein kinase (AMPK) signaling pathway is an important component of this pharmacological activity. Liver kinase B1 (LKB1) acts as a kinase upstream of AMPK and plays an important regulatory role in glucose metabolism. In recent years, as a tumor suppressor, LKB1’s antitumor activity has been widely studied, yet its hypoglycemic activity is not clear. Here, using biochemical and cell viability assays, site-directed mutagenesis, immunoblotting, and immunofluorescence staining, we found that a natural product, antroalbol H isolated from the basidiomycete mushroom Antrodiella albocinnamomea, increases cellular glucose uptake in murine L6 myotubes and 3T3-L1 adipocytes. Of note, our results indicated that this effect is related to LKB1-mediated Thr-172 phosphorylation of AMPKα. Furthermore, we observed that antroalbol H induces the phosphorylation of LKB1 specifically at Thr-189 and changes subcellular localization of LKB1. Finally, antroalbol H treatment strikingly promoted glucose transporter type 4 (GLUT4) translocation to the plasma membrane. We conclude that antroalbol H promotes Thr-189 phosphorylation of LKB1, leading to AMPK activation, revealing this residue as a potential target for increasing glucose uptake, and that antroalbol H therefore has potential for managing hyperglycemia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.RA118.007231Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6615669
- Format
- –
- Schlagworte
- Adipocytes - cytology, Adipocytes - drug effects, Adipocytes - metabolism, AMP-activated kinase (AMPK), Animals, Basidiomycete, Basidiomycota - chemistry, Basidiomycota - metabolism, Biological Products - chemistry, Biological Products - isolation & purification, Biological Products - pharmacology, Cell Line, Cell Membrane - metabolism, diabetes, energy sensing, fungi, Glucose - metabolism, glucose homeostasis, glucose transporter type 4 (GLUT4), Glucose Transporter Type 4 - metabolism, liver kinase B1 (LKB1), Metabolism, Mice, Mutagenesis, Site-Directed, Phosphorylation - drug effects, Protein-Serine-Threonine Kinases - antagonists & inhibitors, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - metabolism, RNA Interference, RNA, Small Interfering - metabolism, sesquiterpene, Threonine - metabolism