title: Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles.
abstract: Salicylate (SAL) has been recently implicated in the antidiabetic effect in humans. We assessed whether 5'-AMP-activated protein kinase (AMPK) in skeletal muscle is involved in the effect of SAL on glucose homeostasis. Rat fast-twitch epitrochlearis and slow-twitch soleus muscles were incubated in buffer containing SAL. Intracellular concentrations of SAL increased rapidly (<5 min) in both skeletal muscles, and the Thr(172) phosphorylation of the α subunit of AMPK increased in a dose- and time-dependent manner. SAL increased both AMPKα1 and AMPKα2 activities. These increases in enzyme activity were accompanied by an increase in the activity of 3-O-methyl-D-glucose transport, and decreases in ATP, phosphocreatine, and glycogen contents. SAL did not change the phosphorylation of insulin receptor signaling including insulin receptor substrate 1, Akt, and p70 ribosomal protein S6 kinase. These results suggest that SAL may be transported into skeletal muscle and may stimulate AMPK and glucose transport via energy deprivation in multiple muscle types. Skeletal muscle AMPK might be part of the mechanism responsible for the metabolic improvement induced by SAL.
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Serizawa
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan. Electronic address: oshima.rieko.37r@st.kyoto-u.ac.jp.
authors.forename: Rieko
authors.initials: R
authors.lastname: Oshima
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Mitsuki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Ichika
authors.initials: I
authors.lastname: Sakon
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kitani
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Goto
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuda
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan. Electronic address: tatsuya@kuhp.kyoto-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013912:Threonine / Q000737:chemistry
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013912:Threonine; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat; D005947:Glucose; D020156:Salicylic Acid
keywords: 5′-AMP-activated protein kinase; Diabetes mellitus; Glucose transport; Insulin signaling; Salicylate; Skeletal muscle