The natural product antroalbol H promotes phosphorylation of liver kinase B1 (LKB1) at threonine 189 and thereby enhances cellular glucose uptake.

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2019
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Abstract
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 , 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 to consequently trigger 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.
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Authors Wang, Fang;Yang, Xiaoyan;Lu, Yanting;Li, Zhenghui;Xu, Yuhui;Hu, Jing;Liu, Jikai;Xiong, Wenyong;
Journal The Journal of biological chemistry
Year 2019
DOI
jbc.RA118.007231
URL
Keywords Keywords not found

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