And no, we are not talking about even more cognitive masturbation and theoretical considerations, here. The conclusions Maria Concetta Miniaci and her colleagues present in the latest issue of Pflugers Arch - Eur J Physiol are in fact based on experimental evidence - experimental evidence that is, if you think it through - not contradicting its practical counterpart!
Evidence from a rodent in vitro study, but evidence of which not just Miniaci et al. (2014) but also I am confirmed that it is relevant for humans, as well.
In a way you may say that Miniaci et al. were inspired by the increased interest in the pro-anabolic effects of blood flow restriction. Corresponding studies using aterial and venous compression, induced by either muscle contraction at high intensity or by pressure cuff will, as the scientists point out, induced "short reduction of blood flow and therefore a reduced delivery of nutrients to the muscle" (Barcroft. 1939; Schwartz. 2000).
"Since glucose is an important energy substrate for skeletal muscle, we presumed that a brief period of glucose deprivation may trigger, as metabolic stress, the anabolic signaling cascade leading to an increased rate of protein synthesis when blood flow recovers and all nutrients are again available (Holloszy. 1996)." (Miniaci. 2014)To test this hypothesis, the scientists investigated the effect of glucose deprivation on mTOR signaling and protein translation in L6 cell line, "a well established in vitro model system for studying skeletal muscle physiology" (Miniaci. 2014); and their results demonstrate that glucose deprivation upregulates mTOR and its downstream target the ribosomal S6 kinase (p70S6K), through the activation of NO/PI3K/Akt/mTOR/p70S6K signaling pathway.
|Figure 1: Glucose deprived and thus stressed muscle cells increase mTOR and p70S6K and show an increase in protein synthesis after only a short time of "running on empty" (Miniaci. 2014)|
mTOR, AMPK, NOS and good (=EU-)stress
In that, auxiliary data from the study at hand showed that the post-workout increase in protein synthesis is directly related to an increase in (surpris!) nitric oxide synthesase activtiy (this is the stuff that is not increased by the mere provision of the NOS substrate arginine, so that corresponding pump-supplements pretty useless). As the Italian researchers point out, NOS is activated in L6 cells exposed to glucose deprivation. Why this is the case, however is still unclear.
"[It] is likely that an increase in AMPK activity, in response to energy depletion, can account for activation of NOS. Indeed, NOS and AMPK can interact through a positive feedback loop. In particular, AMPK has been found to phosphorylate and activate skeletal muscle NOS inducing an increase in glucose uptake." (Miniaci. 2014)If AMPK is in fact the main link, here, the findings of the study at hand, would - just like previous studies on exercise induced increases in glucose uptake lead us back to one surprisingly positive mechanism, which triggers both, glucose uptake and protein synthesis: Metabolic stress! In this case, glucose starvation and susequent acute increases in AMPK expression during exercise.
- Barcroft H, Millen JL (1939) The blood flow through muscle during sustained contraction. J Physiol 97:17–3.
- Holloszy JO, Kohrt WM (1996) Regulation of carbohydrate and fat metabolism during and after exercise. Annu Rev Nutr 16:121–138
- Howarth K, et al (2009). Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery. Journal of Applied Physiology 17:19.
- Lemon, PW, Mullin JP (1980) Effect of initial muscle glycogen levels on protein catabolism during exercise. Journal of Applied Physiology 48:624-629.
- Miniaci, M. C., Dattolo, M. G., Irace, C., Capuozzo, A., Santamaria, R., & Scotto, P. (2014). Glucose deprivation promotes activation of mTOR signaling pathway and protein synthesis in rat skeletal muscle cells. Pflügers Archiv-European Journal of Physiology, 1-10.
- Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661–671.