Carbohydrate ingestion does not alter skeletal muscle AMPK signaling during exercise in humans

Abstract

There is evidence that increasing carbohydrate (CHO) availability during exercise by raising preexercise muscle glycogen levels attenuates the activation of AMPKalpha2 during exercise in humans. Similarly, increasing glucose levels decreases AMPKalpha2 activity in rat skeletal muscle in vitro. We examined the effect of CHO ingestion on skeletal muscle AMPK signaling during exercise in nine active male subjects who completed two 120-min bouts of cycling exercise at 65 +/- 1% V(O2 peak). In a randomized, counterbalanced order, subjects ingested either an 8% CHO solution or a placebo solution during exercise. Compared with the placebo trial, CHO ingestion significantly (P < 0.05) increased plasma glucose levels and tracer-determined glucose disappearance. Exercise-induced increases in muscle-calculated free AMP (17.7- vs. 11.8-fold), muscle lactate (3.3- vs. 1.8-fold), and plasma epinephrine were reduced by CHO ingestion. However, the exercise-induced increases in skeletal muscle AMPKalpha2 activity, AMPKalpha2 Thr(172) phosphorylation and acetyl-CoA Ser(222) phosphorylation, were essentially identical in the two trials. These findings indicate that AMPK activation in skeletal muscle during exercise in humans is not sensitive to changes in plasma glucose levels in the normal range. Furthermore, the rise in plasma epinephrine levels in response to exercise was greatly suppressed by CHO ingestion without altering AMPK signaling, raising the possibility that epinephrine does not directly control AMPK activity during muscle contraction under these conditions in vivo.

Local Nitric Oxide Synthase Inhibition Reduces Skeletal Muscle Glucose Uptake but Not Capillary Blood Flow During In Situ Muscle Contraction in Rats

“…In addition, high levels of the NO donor sodium nitroprusside activate AMPK␣1 in rat skeletal muscle (9). However, in the present study, AMPK activation during contractions, as indicated by AMPK␣ Thr172 phosphorylation (28,29) and ACC␤ phosphorylation, was unaffected by L-NAME infusion (Fig. 5).…”

Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects With Type 2 Diabetes

“…Glucose is another nutrient that could have potentially affected the stimulation of AMPK in the type 2 diabetes group. Akerstrom et al (44) reported that ingestion of a carbohydrate-containing drink, which caused a slight increase in plasma glucose levels, attenuated exercise-induced AMPK activation; yet, this finding was not confirmed by other investigators (45). We previously reported that lean type 2 diabetic subjects with elevated fasting plasma glucose concentrations achieve normal AMPK stimulation with exercise (18).…”

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

“…Unfortunately, it is difficult to determine from our chosen experimental design if the apparent enhanced AMPK signaling (and augmented p53 phosphorylation) in LOW is due to low glycogen per se and/or low circulating glucose availability caused by the absence of CHO feeding before, during, and after exercise. However, it is noteworthy that provision of glucose during exercise also attenuates AMPK activity (2), but this effect is only apparent when glucose feeding spares muscle glycogen utilization (25), thus suggesting that glycogen availability may be the predominant mechanism. We deliberately chose this extreme manipulation of CHO availability so as to initially determine whether there was an actual effect of CHO restriction, although further studies should now attempt to isolate which component of CHO restriction is most dominant.…”