title: Caffeine and contraction synergistically stimulate 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.
abstract: 5'-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr(172) phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser(473) phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction.
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, 606-8501, Japan tsuda.satoshi.55u@st.kyoto-u.ac.jp.
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 Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, 440-0016, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Egawa
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: Rieko
authors.initials: R
authors.lastname: Oshima
authors.affiliation: Key Laboratory of Puer Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, 650201, Yunnan Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
keywords: 5′‐AMP‐activated protein kinase; energy deprivation; glucose metabolism; muscle contraction; muscle fatigue