Caffeine Increases Contraction-Stimulated 5’-AMP-Activated Protein Kinase Activity and Insulin-Independent Glucose Transport in Rat Skeletal Muscle

Abstract

Objective: 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. In this study, we examined the effect of caffeine stimulation on contraction-stimulated AMPK activity and glucose transport.

Materials and Methods: (1) Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mM caffeine for 30 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. (2) 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.

Results: (1) 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. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. (2) 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.

Conclusions: 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.