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Cell volume: The Forgotten Anabolic Stimulus?
The hydration state (cell volume) of muscle cells appears to be an important determinant of protein catabolism, anabolism in health and disease. Increasing muscle cell volume or hydration status acts as an independent anabolic signal as it initiates the cellular mechanisms needed to preserve and create net gains in muscle1.
Very small alterations in cell volume act as separate and potent signals of cellular metabolism. They not only serve to readjust cell volume but also profoundly modify a wide variety of cellular functions2. The effects of cellular hydration are intriguing as an increase in cellular hydration (swelling) acts as an anabolic, proliferative signal, whereas cell shrinkage is catabolic and anti-proliferative1-3.
Cell volume is dynamic and changes within minutes under the influence of substrates, hormones, amino acids, glucose and oxidative stress. Increasing cell volume triggers a number of anabolic reactions such as an increase in amino acid transport and protein synthesis and a decrease in protein catabolism2-4.
Water does not simply reside inside a cell. Osmotic substrates are transported into the cell and this is paralleled by respective water movement across cell membranes and subsequent alterations in cell volume. Pioneering work by serveral research groups in the 90’s provide evidence that glutamine is the most potent amino acid with respect to cell swelling and the influence on cell volume4-6.
Glutamine is the major substrate of the insulin-sensitive Na+-dependant transport system Nm the fastest of all amino transporters in the sarcolemma7. At both basal and insulin-stimulated capacities, glutamine transport into muscle dramatically influences cell volume. Haussinger et al. (1995), using perfused muscle and demonstrated that as long as glutamine concentration remained high, cell volume (and anabolism) remained elevated.
An inverse relationship between protein synthesis rates and cell volume has been established. Using hospital patients with various catabolic conditions, researchers established that the extent of nitrogen wasting correlated closely with muscle glutamine content. Thus, muscle glutamine levels are shown to directly affect cellular volume [Low 6], cell volume is shown to affect protein synthesis rates4,5 and intramuscular glutamine levels also appear to affect protein synthesis8. Only 6-7% of muscle cell glutamine is within bound proteins,9 therefore, changes in cellular hydration state may be the variable linking muscle glutamine content to protein turnover in skeletal muscle and, because of the large mass of skeletal muscle, to whole body nitrogen balance.
What this means to you . . .
Certain proteins and supplements can affect muscle cell volume and anabolic/catabolic responses to training.
Increasing cell volume is an independent anabolic signal. It can be initiated by amino acids such as glutamine and also creatine.
Therefore promoting cell hydration with muscles with strategic supplementation before and in the hours immeidately following intense exercise can enhance muscle anabolism and results from heavy resistance training.
Cell volumizing strategy during intense training programs:
5-10 grams GL-3 Glutamine in the hour before workouts – can be mixed with one serving of VP2 Whey Isolate.
Note: Micronized Creatine should also be used here as creatine is also a known cell volumizer – 5 grams.
5-10 grams GL-3 Glutamine within the hour after workouts – can be mized with one serving of VP2 Whey Isolate.
5-10 grams GL-3 Glutamine within the 3-hour post workout window – can be mized with one serving of VP2 Whey Isolate or Muscle XGF.
Non training days: to maintain elevated cell volume & anabolism, 1 serving (5-10 grams) GL-3 Glutamine per day.
1. Haussinger D, Hallbrucker C, vom Dahl S, Lang F, Gerok W. Cell swelling inhibits proteolysis in perfused rat liver. Biochem J 272: 239-42, 1990.
2. Stoll B, Gerok W, Lang F, Haussinger D. Liver cell volume and protein synthesis. Biochem J 287:217-22, 1992.
3. Haussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 341:1330-1332, 1993
4. Haussinger. D. Regulation of metabolism by changes in cellular hydration. Clin.Nutr 14:4-12, 1995.
5. Vom Dahl S, Haussinger D. Nutritional state and the swelling-induced inhibition of proteolysis in perfused rat liver. J Nutr 126:395-402, 1996.
6. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D. Functional Significance of Cell Volume Regulatory Mechanisms Physiol Rev. 78:247-272, 1998.
7. Low SY, Taylor PM, Rennie MJ. Response of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J Physiol 492:877-885, 1996.
8. Cribb PJ, Williams AD, Hayes A and Carey MF. The effect of whey isolate on strength, body composition and plasma glutamine. In J Sports Nutr Exerc Metab, 2006.
9. Curi R, Lagranha CJ, Doi SQ. Molecular mechanisms of glutamine action. J Cell Physiol 204: 392-401, 2005.