October 11, 1999 (Volume 2,
Number 17)
Research Update
by Bryan Haycock MSc., CSCS
bryan@thinkmuscle.com
Please send us your feedback on
this article.
As we approach the new millennium we find the science of building
muscle progressing faster than ever before. Long gone are the days of
simple trial and error when it comes to building muscle. The modern
bodybuilder demands more than just "hear say" if they are to adopt a new
training routine or nutritional supplement. This column was created to
keep today’s bodybuilder on the cutting edge of scientific research that
might benefit them in their quest for body perfection.
New study shows mixed drinks and muscle growth just
don’t mix.
Title:
Inhibition of muscle protein synthesis by alcohol is
associated with modulation of eIF2B and eIF4E
Researchers:
Lang, Charles H., Wu D., Frost RA., Jefferson
LS., Kimball SR., and Vary TC.
Departments of Cellular and Molecular Physiology and Surgery,
Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033
Source:
American Journal of Physiology 277 (Endocrinol.
Metab. 40): E268–E276, 1999.
Summary:
The present study examined potential mechanisms for the inhibition of
protein synthesis in skeletal muscle after chronic alcohol consumption.
Rats were maintained on an alcohol-containing diet for 14 wk; control
animals were pair fed. Alcohol-induced myopathy was confirmed by a
reduction in lean body mass as well as a decrease in the weight of the
gastrocnemius and psoas muscles normalized for tibial length. No
alcohol-induced decrease in total RNA content (an estimate of ribosomal
RNA) was detected in any muscle examined, suggesting that alcohol reduced
translational efficiency but not the capacity for protein synthesis. To
identify mechanisms responsible for regulating translational efficiency,
we analyzed several eukaryotic initiation factors (eIF). There was no
difference in the muscle content of either total eIF2a or the amount of
eIF2a in the phosphorylated form between alcohol-fed and control rats.
Similarly, the relative amount of eIF2Be in muscle was also not different.
In contrast, alcohol decreased eIF2B activity in psoas (fast-twitch) but
not in soleus or heart (slow-twitch) muscles. Alcohol feeding also
dramatically influenced the distribution of eIF4E in the gastrocnemius
(fast-twitch) muscle. Compared with control values, muscle from
alcohol-fed rats demonstrated 1) an increased binding of the translational
repressor 4E-binding protein 1 (4E-BP1) with eIF4E, 2) a decrease in the
phosphorylated g-form of 4E-BP1, and 3) a decrease in eIF4G associated
with eIF4E. In summary, these data suggest that chronic alcohol
consumption impairs translation initiation in muscle by altering multiple
regulatory sites, including eIF2B activity and eIF4E availability.
Discussion:
By analyzing the complex series of steps by which our muscle cells
build new proteins we realize that there are many stages in this process
where protein synthesis could be modulated. For a more detailed treatment
of the steps involved in protein synthesis please refer to
November 1, 1998 installment of Research
Update in Mesomorphosis Volume 1, Number 7.
From the study above we see that it is translation inhibition that is
responsible for the decline in protein synthesis rates seen with alcohol
use. This is similar to the mechanism by which exercise inhibits protein
synthesis during your workout. Initiation of translation (the binding of
mRNA to the ribosomal pre-initiation complex) requires group 4 eukaryotic
initiation factors (eIFs). These initiation factors interact with the mRNA
in such a way that makes translation (the construction of new proteins
from the mRNA strand) possible. Two eIFs, called eIF4A and eIF4B, act in
concert to unwind the mRNA strand. Another one called eIF4E binds to what
is called the "cap region" and is important for controlling which mRNA
strands are translated and also for stabilization of the mRNA strand.
Finally, eIF4G is a large polypeptide that acts as a scaffold or framework
around which all of these initiation factors and the mRNA and ribosome can
be kept in place and proper orientation for translation.
Now it is eIF4E that appears to be a key point for modulation of
translation, or protein synthesis. eIF4E (at the mRNA cap) binds with
eIf4G (scaffold) in order to form the functional complex (eIF4F) that
allows translation of the mRNA. Some research shows that eIF4E activity is
modulated by increased phosphorylation of the eIF4E molecule, which in
turn increases its binding affinity for the mRNA cap region. This would
effectively increase the amount of translation going on and ultimately the
amount of protein synthesis. Another explanation involves a "binding
protein" called 4E-BP1. It binds the eIF4E molecule making it unable to
bind to eIF4G. This effectively would put a stop to the whole process. In
the study above it was shown that alcohol increases the binding of 4E-BP1
to eIF4E. Alcohol was also shown to decrease the phosphorylated g-form of
4E-BP1, and decrease the concentration of eIF4G associated with eIF4E. All
of this adds up to an inhibition of muscle growth and even an increase in
muscle protein breakdown.
Bodybuilders are known to go to great lengths to ensure maximal rates
of muscle growth, sometimes even engaging in absurd or even dangerous drug
regimens. If they are willing to go to so much trouble, I don’t understand
why some still engage in frequent and substantial alcohol consumption.
Perhaps it has to do with their personalities. Either way, drinking and
muscle growth simply do not mix. You may argue that a drink now and then
will not make a difference. I could argue that an extra set or a second
scoop of protein won’t make much difference either but I’m sure you
wouldn’t hesitate to take those steps to ensure maximum gains. Even though
an occasional drink may not throw your gains completely down the crapper,
as long as the alcohol is in your system you are NOT growing. Sometimes
going the extra mile to do everything you can to be successful gives you
that tiny edge over your competitors who were more laxed in the
preparations.
Exercise and Diabetes: Long held views of how
exercise effects glucose uptake give way to more correct thinking.
Title:
Effect of tension on contraction-induced glucose
transport in rat skeletal muscle
Researchers:
Jacob Ihlemann, Thorkil Ploug, Ylva Hellsten,
and Henrik Galbo
Copenhagen Muscle Research Center, Rigshospitalet, and Department of
Medical Physiology, The Panum Institute, University of Copenhagen, 2200
Copenhagen N, Denmark
Source:
Am J Physiol Endocrinol Metab 277(2):E208-E214
Summary:
These researchers questioned the general view that contraction-induced
muscle glucose transport only depends on stimulation frequency and not on
workload. Incubated soleus muscles were electrically stimulated at a given
pattern for 5 min. Resting length was adjusted to achieve either no force
(0% P), maximum force (100% P), or 50% of maximum force (50% P). Glucose
transport (2-deoxy-D-glucose uptake) increased directly with force
development [27 ± 2 (basal), 45 ± 2 (0% P), 68 ± 3 (50% P), and 94 ± 3
(100% P) nmol × g1 ×
5 min1]. Glycogen decreased at 0% P but did not change further with force
development. Lactate, AMP, and IMP concentrations were higher and ATP
concentrations lower when force was produced than when it was not.
5'-AMP-activated protein kinase (AMPK) activity increased directly with
force [20 ± 2 (basal), 60 ± 11 (0% P), 91 ± 12 (50% P), and 109 ± 12 (100%
P) pmol × mg1 ×
min1]. Passive stretch (~86% P) doubled glucose transport without altering
metabolism. In conclusion, contraction-induced muscle glucose transport
varies directly with force development and is not solely determined by
stimulation frequency. AMPK activity is probably an essential determinant
of contraction-induced glucose transport. In contrast, glycogen
concentrations per se do not play a major role. Finally, passive stretch
per se increases glucose transport in muscle.
Discussion:
Exercise can serve as a powerful tool in the management of diabetes.
Physical activity in the form of a structured exercise program can have a
pronounced effect on carbohydrate metabolism as well as lipid metabolism.
It can also have beneficial effects on disorders associated with diabetes
such as obesity, dyslipoproteinaemia, and high blood pressure. Exercise,
by helping to regulate blood glucose levels, my also serve to postpone the
onset of disorders associated with microvascular disease such as
neuropathy, nephropathy, and retinopathy. Thus a structured exercise
program has the potential to be a valuable tool in the management of
diabetes.
Several studies have shown the beneficial effects of exercise on
glycemic control in diabetics. This effect appears to be the result of
mechanical and/or metabolic activity of exercising muscle tissue. During,
and for a short period after, an acute bout of exercise of moderate
intensity, glucose uptake is enhanced in skeletal muscle. This is referred
to as non-insulin dependant glucose up take. Muscle contractions and
insulin cause the translocation of the GLUT4 glucose transporter proteins
to the plasma membrane and transverse tubules. The subcellular origin of
the GLUT4-containing vesicles is not clear, but exercise and insulin
appear to recruit distinct GLUT4-containing vesicles, and/or mobilize
different pools of GLUT4 proteins. Insulin-stimulated GLUT4 translocation
involves IRS-1 and PI 3-kinase, and the redistribution of Rab4 (a molecule
specific to insulin stimulated GLUT4 translocation). Exercising muscle
utilizes a phosphatidylinositol 3-kinase and MAP kinase-independent
mechanism and does not result in the redistribution of Rab4. It has been
thought that the contraction signal is probably initiated by the release
of calcium from the sarcoplasmic reticulum and may involve and
autocrine/paracrine mechanism (e.g. nitric oxide, adenosine, bradykinin),
protein kinase C, or a combination of these and other currently unknown
factors.
The study we look at today shows us some very important things about
what is responsible for the increase in glucose uptake by skeletal muscle
following exercise. The major findings are that at a given frequency of
contractions glucose transport varies directly with developed force. For
decades it has been believed that contraction-induced glucose transport is
determined only by the frequency with which muscle is stimulated and not
by mechanical loading. You will see evidence of this belief in the current
protocols used for treatment of diabetics with high volume, low intensity
endurance exercise.
It has been observed previously that glycogen content and glucose
uptake are inversely related. It is believed that glucose transporters are
liberated from the golgi vesicles in response to the breakdown of glycogen
molecules. In the present study there were no significant differences in
glycogen levels between groups, however, glucose transport was 300%
greater despite equal glycogen stores, in the high tension group.
Finally, an interesting finding was that passive stretch also caused an
increase in glucose uptake. It is known that intracellular Ca+
concentrations have an effect on glucose transport. It was thought that
sarcolemmal damage may have caused calcium ions to flood the intracellular
space giving rise to increased glucose transport. This tuned out not to be
the case. The ability of simply stretching a muscle to cause glucose
uptake remains to be explained.
The results of this study along with other recent research showing
resistance exercise to in fact be superior for increasing muscle glucose
uptake needs to be considered when prescribing exercise for diabetic
patients. This information should also be useful to diabetics who
currently enjoy bodybuilding or other strength sports.
References:
Eriksson, J. Aerobic endurance exercise or circuit-type resistance
training for individuals with impaired glucose tolerance? Horm Metab
Res 1998 Jan;30(1):37-41
Have doctors been exaggerating the effect of
steroids on your liver?
Title:
Anabolic steroid-induced hepatotoxicity: is it
overstated?
Researchers:
Dickerman RD, Pertusi RM, Zachariah NY, Dufour
DR, McConathy WJ
The Department of Biomedical Science, University of North Texas Health
Science Center, Fort Worth 76107-2699, USA.
Source:
Clin J Sport Med 1999 Jan;9(1):34-9
Summary:
Subjects: The participants were bodybuilders taking self-directed
regimens of anabolic steroids (n = 15) and bodybuilders not taking
steroids (n = 10). Blood chemistry profiles from patients with viral
hepatitis (n = 49) and exercising and non-exercising medical students
(592) were used as controls.
Measurements: The focus of the blood chemistry profiles was on
aspartate aminotransferase (AST), alanine aminotransferase (ALT),
gamma-glutamyltranspeptidase (GGT), and creatine kinase (CK) levels. (All
indicators of liver function.)
Results: In both groups of bodybuilders, CK, AST, and ALT
were elevated, whereas GGT remained in the normal range. In contrast,
patients with hepatitis had elevations of all three enzymes: ALT, AST, and
GGT. Creatine kinase (CK) was elevated in all exercising groups. Patients
with hepatitis were the only group in which a correlation was found
between aminotransferases and GGT.
Discussion:
All in all this study was pretty straight forward. It set out to see if
markers other than aminotransferase (AST) of liver function were
correlated with steroid use in bodybuilders. In this study we saw the
comparison of blood samples from steroid using bodybuilders, non-steroid
using bodybuilders, med students, and patients with hepatitis. Several
indicators of liver function were measured wich included aspartate
aminotransferase (AST), alanine aminotransferase (ALT),
gamma-glutamyltranspeptidase (GGT), and creatine kinase (CK) levels.
Creatine kinase is a common blood marker of muscle damage and thus it was
elevated in those subjects who exercised. The other markers have normal
values as well in healthy subjects (see table 1). I include a table of
normal ranges for these markers simply to give you some idea of what your
particular blood test results mean if you should have them done while on a
cycle. And yes, if you are lucky enough to have a doctor who is willing to
monitor your health knowing you are using anabolics please have your blood
work done before, during, and after your cycles.
Table 1.
