Premium
Anti‐cancer drug F‐59 regulates glucose metabolism through AMPK
Author(s) -
Song Parkyong,
Kim Jong Hyun,
Suh Phannghill,
Ryu Sungho
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb120
Subject(s) - ampk , chemistry , glucose uptake , glucose transporter , glucose homeostasis , protein kinase a , carbohydrate metabolism , amp activated protein kinase , energy homeostasis , endocrinology , medicine , pharmacology , biochemistry , kinase , insulin , insulin resistance , biology , receptor
AMP‐activated protein kinase has been described as a key signaling protein which can regulate whole body energy homeostasis. AMPK enhances catabolic pathway such as glucose and fatty acid metabolism in response to increased energy deprivation and switches off protein, carbohydrate and lipid biosynthesis. To identify novel chemical agonist of AMPK, we carried out drug library screening through cell based system. As a result, anti‐cancer drug F‐59 phosphorylates AMPK and downstream substrate ACC in 3T3L1 adipocytes and L6 myoblast. Glucose uptakes are induced by F‐59 alone treatment and co‐treatment with insulin synergistically in differentiated L6 myotube. The inhibition of AMPK by chemical inhibitor, compound C abolishes F‐59 mediated glucose uptake. Furthermore, administration of F‐59 to mouse significantly decreased the fasting plasma glucose concentration with does dependent manner. And finally, we characterized that AMPK can be modulated by reactive oxygen species (ROS) and free radical scavenger, N‐acetylcystein (NAC), reversed the effects of F‐59 on glucose levels. This could suggest that F‐59 can regulate glucose homeostasis in vivo and represent therapeutic potential in Type 2 diabetic model.