Insulin's anabolicity

K

Karky

2
I would like to write and get input on something about insulin's anabolicity (yes, I just made that word up)

in the last year or so I've begun to move away from the understanding of insulin as one of the most potent anabolic hormones. It seems that it's written everywhere how much it stimulates protein synthesis, etc.. but does it? I've never quite understood where the statement that insulin is such a powerful anabolic hormone (for muscle, mind you) comes from.

According to this review:

it doesn't. It only has an effect on protein breakdown:
There is no doubt, however, that insulin markedly inhibits
human muscle protein breakdown. This process seems to be
exquisitely sensitive, with most of the inhibition breakdown
occurring at plasma levels of insulin between those seen in
an overnight fast and after a small meal, i.e. in the range of
0–15 m-units/l [12].
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The review also states that insulin, GH or IGF' short term effects are not needed for amino acids to have a maximal effect on protein synthesis.

I thought that maybe the thought that insulin stimulated protein synthesis came from the "insulin shuttles amino acids into muscle" thing.. but it turns out that it's extracellular, not intracellular amino acids that stimulate protein synthesis. (I can dig up references here if you want) Of course, you need amino acids inside the muscle cells as substrates for anabolism, but is the limiting step here the transport of amino acids across the cell membrane?

thoughts?
 
Am J Physiol Endocrinol Metab (May 16, 2006). doi:10.1152/ajpendo.00003.2006
This Article



Mechanism of Insulin's Anabolic Effect on Muscle - Measurements of Muscle Protein Synthesis and Breakdown Using Aminoacyl tRNA and Other Surrogate Measures
Lisa S Chow1, Robert C Albright2, Maureen L Bigelow1, Gianna Toffolo3, Claudio Cobelli3, and K. Sreekumaran Nair1*
1 Division of Endocrinology, Nutrition and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
2 Division of Nephrology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
3 Department of Information Engineering, University of Padova, Padova, Italy



Despite being an anabolic hormone in skeletal muscle, insulin's anti-catabolic mechanism in humans remains controversial with contradictory reports showing either stimulation protein synthesis (PS) or inhibition protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of amino acyl tRNA and intracellular pool. We report insulin's effect on muscle protein turnover using amino acyl-tRNA as the precursor of PS and PB is calculated by mass balance of tracee amino acid (AA). We compared the results calculated from various surrogate measures. To determine the physiological role of insulin on muscle protein metabolism we infused tracers of leucine and phenylalanine into 18 healthy subjects and after a three hours, 10 subjects received a four hour femoral arterial infusion of insulin (0.125 mU/kg/min) while eight subjects continued with saline. Tracer to tracee ratios of leucine, phenylalanine and ketoisocaproate were measured in the arterial and venous plasma, muscle tissue fluid and AA-tRNA to calculate muscle PB and PS. Insulin infusion, unlike saline, significantly reduced the efflux of leucine and phenylalanine from muscle bed based on various surrogate measures which agreed with those based on leucyl-tRNA (-28%) indicating a reduction in muscle PB (P<0.02) without any significant effect on muscle PS. In conclusion, using amino-acyl tRNA as the precursor pool, it is demonstrated that in healthy humans in the postabsorptive state, insulin does not stimulate muscle protein synthesis and confirmed that insulin achieves muscle protein anabolism by inhibition of muscle protein breakdown.
 
thanks, I'll read through that.

It's weird how they first say that "Despite being an anabolic hormone in skeletal muscle, insulin's anti-catabolic mechanism in humans remains controversial"
then they find that it's anticatabolic but not anabolic (though that depends on what you mean by anabolic.. as something that reduces catabolism is, in effect, anabolic)
 
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Karky said:
thanks, I'll read through that.

It's weird how they first say that "Despite being an anabolic hormone in skeletal muscle, insulin's anti-catabolic mechanism in humans remains controversial"
then they find that it's anticatabolic but not anabolic (though that depends on what you mean by anabolic.. as something that reduces catabolism is, in effect, anabolic)
Click to expand...

This is where my opinion has always been with what I've read. It's been a while since I've dug up research, but it's hard to go against the real world evidence of the people I see using insulin to gain mass..
 
yeah, but people who use exogenous insulin, do they use supraphysiological levels? maybe that comes into play? Maybe it really shuts down protein breakdown?
 
I thought I'd dig up this one again as I found something interesting:


Whereas insulin has long been recognized as an important anabolic hormone, its specific role in regulation of MPS in human subjects has been the subject of debate. Whereas in vitro experiments have clearly demonstrated a stimulatory effect of insulin on MPS, studies in human subjects have yielded inconsistent results (see Ref. 18 for review). However, when the role of amino acid concentrations in the regulation of MPS is considered, the apparently contradictory in vivo results can be largely reconciled. When glucose/insulin are given alone, such as during the euglycemic/hyperinsulinemic clamp procedure, plasma amino acid levels fall. The effect of a reduction in amino acid levels was discussed above. Thus, although insulin itself has a stimulatory effect on synthesis, an adequate eIF2B activity is required for that potential effect to translate into an increased rate of synthesis, and this is not the case when amino acid levels fall. Consequently, studies in which plasma amino acid levels were allowed to drop during insulin infusion have generally failed to show a stimulatory effect of insulin on MPS. In contrast, when the effect of insulin has been assessed in the context of maintained (e.g., Ref. 19 ) or elevated (e.g., Ref. 20 ), concentrations of amino acids have been found to stimulate synthesis. Thus, the interactive response of MPS to carbohydrate plus amino acids described above can be predicted, although carbohydrate intake alone has minimal effect.
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very interesting if you ask me! Still seems as if amino acids are the chief when it comes to regulating protein synthesis, though.
 
Damn, I want to reply to this but I have to go home. Hopefully I'll be on later with some wisdom (there's always a first time :D)
 
Karky said:
(though that depends on what you mean by anabolic.. as something that reduces catabolism is, in effect, anabolic)
Click to expand...

Hmm, anabolic means that it creates or promotes an increase in mass, I would have thought that reducing catabolism doesn't count although the effect is the same.

Having said that, by promoting Glycogen storage, Insulin must surely be said to have a strong anabolic effect. Is this not true?
The insulin is needed to get enough glycogen into the muscles to initiate protein synthesis, therefore it has a direct influence on 'anabolicity' (if it isn't a word it should be :))

Sorry if that sounds a bit basic but that was my understanding
 
Do you mean that glycogen stores promote anabolism? Glycogen stores don't initiate protein synthesis.
Or that the storage of glycogen in itself is anabolism? Since the last one is true (I'm sure the former is too, but I don't know of any specific pathways that could mediate that response.. perhaps cell stretching)
When I anabolism anabolism here I mean contractile filament (actin and myosin) growth.. since fat growth is anabolism too :p
 
Not promote protein synthesis exactly, but it's a requirement for it to take place isn't it? If the muscles don't recover glycogen stores then protein synthesis doesn't take place so Insulin plays a pivotal role.
 
protein synthesis can occur with depleted levels of glycogen. And you don't need high levels of insulin to store glycogen in muscles (though glycogen synthesis can go faster with higher levels of insulin).
 
OK, I should have said that protein synthesis would be sub-optimal. Would the increase in protein synthesis caused by the presence of Insulin not make it anabolic in terms of muscle development? Or is it just semantics?

Page 134 on this study has a good bit to read on the subject

On the right hand of the page it has a bit called 'types of supplementation affecting protein sysnthesis'. The whole this is very interesting to read too though.
 
but what we are discussing here is if insulin has any effect on protein synthesis. Some studies where they measured protein synthesis before and after insulin infusion found no difference.

In that review they use carbs, not insulin, so you can't say from that that insulin actually caused the increase in protein synthesis, or if it was some other effect of the carbs. They just assume it was the insulin since insulin is widely known as a very anabolic hormone for muscle tissue, which is the dogma that I'm challenging here. However, the new stuff I found suggests that insulin is anabolic as long as amino acids are kept at the same level before and after insulin infusion.
 
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Matt, about BBers using insulin, here's something interesting:


studying a 1000 fold increase in insulin.

I changed the link from what I used in your PM, as in your PM it was link to a site talking about the study and the site was kind of full of steroid stuff, so I figured the link to the journal would do better on the forum :p
 
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Karky said:
Matt, about BBers using insulin, here's something interesting:


studying a 1000 fold increase in insulin.

I changed the link from what I used in your PM, as in your PM it was link to a site talking about the study and the site was kind of full of steroid stuff, so I figured the link to the journal would do better on the forum :p
Click to expand...

I can't get the link to work

EDIT: Oops, works now
 
I like this part :-

The high levels of insulin used in this study are not practical for bodybuilders to consider using. The subjects blood glucose was kept constant through artificial means to prevent hypoglycemic coma. In other words kiddies, DON'T TRY THIS AT HOME! Besides the danger involved with raising insulin levels 1,000 times above normal without a controlled infusion of glucose, it isn't really necessary if you want to get an anabolic response. Think of what was done in this study like flooding the basement in order to water the lawn. The anabolic effects produced in this study were most likely due to excess insulin binding to hybrid IGF-1 receptors. The same effect through can be achieved without all the insulin by simply adding a little IGF-1. After all, you should always use the right tool for the job.
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Insulin is my favorite hormone, sure it can store some fat.. But all I need is a bunch of candy and choc milk and BBOOOOMMM insulin surge!
 
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