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


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 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 AMPK?. 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.

SUBMITTER: Wang F 

PROVIDER: S-EPMC6615669 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Wang Fang F   Yang Xiaoyan X   Lu Yanting Y   Li Zhenghui Z   Xu Yuhui Y   Hu Jing J   Liu Jikai J   Xiong Wenyong W  

The Journal of biological chemistry 20190521 27


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  ...[more]

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