Why Insulin works:
Androgen/Insulin Synergy
By Michalovich Greutstein
I’m taking it you want me to go paragraph by paragraph through this article…. I don’t have a lot of time today, but I’ll tell you what I think as best I can
Should anabolics be used with insulin or is it best to use insulin while off steroids in order to hold onto muscle mass?
We are going to demonstrate that they have to be used together. We will also try to provide some clues about their respective contribution to the synergy both hormones create. This will help us to handle both drugs better.
Here are some general observations:
It is safe to conclude something else is needed to uncover the full anabolic effect of steroids. The hormone which is the most affected by a high calorie or by a low calorie diet is insulin.
This is not true. Insulin release is stimulated by BLOOD GLUCOSE---which is most affected by carbohydrates in the diet. Obviously, simple will change blood glucose more rapidly than complex carbohydrates, but overall carbohydrates have the biggest influence on blood glucose levels because they all break down to glucose. Second is protein intake. Amino acids can be directly converted to glucose, thus stimulating insulin release. Finally is fat, which because of the multistep process to degrade to glucose, actually has the least direct effect on blood sugar levels. Total caloric intake really doesn’t have that much to do with it. Its possible to eat a very high fat diet with a HUGE number of calories and have a relatively low insulin secretion level. That’s why high fat diets are fed to humans and animals (like ferrets) with insulin producing pancreatic (Insulinoma) tumors. Daily caloric needs can be met without inducing oversecretion of insulin from the tumor cells.
Also, heavy steroid users know that past a certain amount of steroids, adding insulin will make a big difference as far as muscle gains are concerned. Insulin is thus a strong candidate as a potentiator of anabolic steroids (which we will indiscriminately refer to as androgens, steroids or anabolics).
Um…. No. This is backwards. Anabolic steroids (specifically testosterone has an insulin sensitization effects TO A CERTAIN LEVEL after that point anabolic steroids will actually decrease the effects of insulin by inducing insulin resistance. The best real world example of this are Type II diabetics who have low testosterone levels. They go on HRT, their testosterone levels return to normal and their diabetic medication needs reduce significantly. When I personally started HRT, as my test levels returned to normal, insulin needs decreased by up to 5 units per day and my HBA1C dropped by 0.5 without a significant change in diet or exercise. This is HUGE and a point I discussed with my endocrinologist in detail. The thing is as serum Test levels increase, the body tries to maintain homeostasis by down regulating insulin receptors. This leads to loss of insulin sensitivity---that’s why you don’t’ see animals or humans with Leydig cell tumors or in animals with steroidiogenic adrenal tumors. Again ferrets are a prime example of this because the specific type of adrenal tumor secretes sex hormones. It’s also thought (but not proven) that this may lead to stimulation of insulin secreting tumors in American ferrets with concurrent adrenal disease. This explains the reason its very rare to see a bilateral adrenal tumor who also doesn’t have concurrent insulinomas. Again, this isn’t proven, but it makes sense physiologically. This may also be a reason humans taking huge doses of anabolics---not including GH, which has proven insulin desensitizing effects—can “get by” with taking insulin without seeing huge negative effects. They have induced a degree of insensitivity, that they are compensating for with exogenous insulin. THIS ALSO HAS NOT BEEN PROVEN. This is one of my own thoughts.
Furthermore, studies performed in trained dogs have shown a lack of insulin completely negates the anabolic effects of steroids on protein synthesis. There are some easy hypotheses such as a possible androgen receptor up regulation, a stimulation of androgen secretion, an antiaromatase effect arising from insulin. But, there is still something missing.
References please. This is not something I’m aware of in the veterinary literature and I’d really like to read the paper based on how Im reading its presentation here…
That said, this is also a no brainer statement warping the basic effects of anabolic steroids and insulin both. Think about it, what happens with a diabetic dog who needs insulin and doesn’t get it? That dog will have muscle wasting due to ketoacidosis just like a diabetic human. The body isn’t getting the glucose it needs, so it goes into starvation mode, burning stored fat and muscle for energy.
Using anabolics plus insulin will not make you much bigger unless you weight train. The synergy can only be realized if insulin + steroids + training are present. What is the link between those three factors?
This is a nobrainer statement used to justify the addition of insulin. You see these all the time in latenight “infomercials”. The bottom line is YOU WON”T GAIN MUSCLE UNLESS YOU WEIGHT TRAIN. Duh….. This statement really has no purpose other than to justify the ideas that are being presented.
A very likely candidate is an enzyme called insulinase. As its name implies, it is an enzyme responsible for the destruction of insulin. But we are going to see it does much more than that.
It is found inside many tissues of the body, particularly in muscle.
This is not true. The bodies primary regulatory mechanism with insulin is to downregulate its uptake and to increase free circulating blood glucose. This is done by epinephrine, glucagon, cortisol, and GH.
Epinephrine's actions are mediated through adrenergic receptors. Epinephrine is a non-selective agonist of all adrenergic receptors including α1, α2, β1, and β2 receptors. Activation of these receptors leads to release of stored glycogen from muscle and liver cells and to a degree downregulation of insulin receptors.
Glucagon is secreted by the alpha cells of the pancreas and has in essence the exact opposite effect of insulin—it stimulates epinephrine release, stimulates glycogen breakdown, and fat breakdown. Glucagon is the hormone given to people in a severe hypoglycemic crisis that will save their lives because it returns blood glucose to normal levels.
Cortisol does not have a direct effect on insulin, but it does cause increased glucose production by the liver and glycogen breakdown. It also mobilizes extrahepatic amino acids and ketone bodies which are metabolized to glucose. There is some misinformation about cortisol because it directly has no effect on insulin, however its metabolite, cortisone will greatly inhibit insulin receptor binding, also increasing blood glucose levels.
GH inhibits insulin receptors, causing a down regulation of insulin uptake. Generally I think of GH being increased AFTER the hypoglycemic episode as the bodies response to replenish what was utilized during the hypoglycemia. It increases gluconeogenesis, amino acid uptake, and lypolysis. This replenishes stored glucose reserves.
Insulinase is a misnomer. Insulin degradation occurs in the liver by a group of M16A metalloproteases. The specific enzyme with the most insulin degradation activity is the one known as Insulin Degrading Enzyme. This enzyme has a direct effect on the Beta chain of the insulin molecule, cleaving it, thus inactivating the insulin molecule. This enzyme is located in largest concentrations in the liver as part of the M16A metalloprotease group.
What science is telling us is that insulinase is essential for insulin to provide its anti-catabolic effect on our muscles. It is also likely that insulinase is able to multiply the anabolic effects of androgens. It's worth repeating: insulin cannot stop protein catabolism without insulinase and the effects of steroids are potentiated by insulinase. It sure looks good.
No. not the science I know. Again, read what I’ve posted above.
Androgens are very powerful stimulators of the muscle protein synthesis rate. On the other hand, the muscle gains provided by androgens do not match this elevation in synthesis. steroids promote anabolism to a much higher rate than they make our muscles grow.
This paragraph is circular and contradicts itself as I’m reading it.
The reason for this discrepancy is that they also stimulate protein degradation. I know many people think they are anti-catabolic, but it is not the case. Anabolics stimulate protein turnover. This means they increase both synthesis and degradation of proteins. They are simply more effective at stimulating synthesis than degradation, which is why they make our muscles grow but not at a super fast rate. Look at how long it takes to grow huge muscles. If androgens were stimulating synthesis while inhibiting degradation, one would grow very, very quickly.
The problem with this is the mixing of ANDROGEN with ANABOLIC terminology. Those are really two different functions.
Anabolic steroids have two basic functions…the are anabolic, which means they promote cellular growth and they are androgenic, which means they promote masculinization.
The end result of the combination of these effects—which directly comes from the anabolics relationship to testosterone and the association with testosterone specific receptors is increased muscle mass and masculinization effects (ie a male becomes more male and a female becomes more male).
This is where insulin comes in. As we said, it mostly reduces protein degradation rate. It might stimulate protein synthesis right after training, but this effect is very limited in duration. Ideally, using insulin along with steroids would allow us to accelerate synthesis (thanks to anabolics) and reduce degradation (thanks to insulin). This is the best way to grow muscle fast.
Again, this is confusing and poorly written. Insulin is the hormone that controls glucose metabolism, which provides a cell with ENERGY. The uptake of amino acids associated with insulin is more involved with energy metabolism and maintenance of the cellular function than it is with growth. Anabolic steroids promote aminoacid uptake specifically for growth.
Unfortunately, as both insulin and anabolics need insulinase to work better, they will compete against each other for this enzyme. For natural athletes, the supply of muscle insulinase should roughly meet the demand. Now if you add anabolics, there will be less insulinase for insulin. If you do not take too high a dose of steroids, the level of insulinase should still be sufficient to allow a fair insulin-induced anti-catabolism. But as you take more steroids, the insulinase available for insulin will be lower and lower
This paragraph makes no sense to me. See what I posted above about insulin metabolism.
.
Insulin will lose its anti-catabolic effect. As it will still bind some insulinase, the enzyme availability for steroids will not be optimal either. Anabolics will lose some of their potency.
Again, these statements make no sense physiologically. Anabolic steroids cause decreased sensitivity not because of increased insulin breakdown but because of downregulation of insulin receptors at high doses. At this point, I’m beginning to wonder if the author of this article really has even the slightest clue how insulin works or what it does and instead is just spouting trying to justify this thought on an enzyme that doesn’t function the way they are trying to present it.
What is important to understand is that past a certain dose, anabolics will provide their own antidote against muscle growth. The only solution (beside using less steroids) is to increase insulinase level.
At least two factors can accomplish this feat:
The first one is insulin itself. The higher the insulin level is in a target organ (muscle for example) the higher the insulinase level will be. You would expect that the body would detect the shortage of insulinase for insulin and so produce more insulin (or more insulinase).
Again, this shows no understanding of basic physiology. Insulin degredation occurs in the liver, not in some random target organ. Insulin that is taken up---ie it binds to an insulin receptor one of two things happens. Its taken into the cell where it undergoes degration by M16A metalloproteases or it is released back into circulation where it is transported to the liver where its taken up and degraded by IDE.
Unfortunately, this does not seem to be the case. While insulinase is crucial for the anti-catabolic effect of insulin, it does not seem as important for glucose disposal.
Insulin's main function is not to assist in muscle growth but to control glucose homeostasis. As a result, it is likely our body does not really care about a relative shortage of insulinase. In any case, we are left with a less than optimal equilibrium. It is up to the bodybuilder to react to this imbalance.
This paragraph contradicts paragraphs above. It is correct in saying that insulins primary function is glucose metabolism though…
One way of increasing insulin secretion is to eat more, but you can only do so up to a point. You cannot increase your carb intake in parallel with the amount of steroids without getting too fat. Another solution is to use drugs to add or to stimulate insulin secretion. This way you get the insulin without the excess of calories.
In any case you now understand why steroids work better while on a high calorie diet while they lose their potency during a diet or a shortage of insulin.
All I can say to this paragraph is UH?
Here is a way of "artificially increasing insulin level": One dose of long acting insulin first thing in the morning (this is the only injection). Before each meal (except the pre-workout one), take a sulfonylurea (an oral anti-diabetic drug which will boost food induced insulin secretion ). I like Glipizide because of its short half-life. In case you experience hypoglycemia, you know it will not last. This is the main problem with the long acting sulfonylureas. When you are hypoglycemic, you try to compensate by absorbing carbs. But the drug will make your pancreas secrete even more insulin before the carbs can hit the blood. It makes the hypoglycemia worse - not better.
Ok, first taking a long acting insulin will not do shit through the day for a nondiabetic in terms of insulin metabolism. What will happen is the body will sense the insulin lowering effects and as a result not be stimulated to secrete as much insulin in response to dietary intake through the day. If there is an episode of hypoglycemia, then the body will release epinephrine, glucagon, and cortisol.
Oral antidiabetic medications, such as glipizide are quite capable of inducing fatal hypoglycemia. To say that the hypoglycemia is OK because “of the short half life”, “you know it will not last” is ridiculous in my opinion. Hypoglycemia induces epinephrine and cortisol secretion leading to glycogen breakdown long before the effects become fatal. This will inhibit weghttraining gains. Not only that, but even short term loss of fuel for the brain will result in death. If the brain doesn’t have the fuel it needs, its not going to function. Then you die.
In case of problems, make sure you get some ready-to-inject Glucagon (sold as "insulin emergency kits" in drugstores). An additional benefit of the Glipizide is that it induces the release of GH on top of insulin which is beneficial for non diabetics. This is a nice way to fix the reduced anticatabolic property of insulin. Unfortunately, this will not yet provide the optimal amount of insulinase to have steroids work better.
WRONG. Glipizide will only induce GH release if it induces hypoglycemia. This drug has no effect on GH outside of its ability to induce hypoglycemia.
We said that training was the third key ingredient in this synergy. This is because training can stimulate insulinase activity. Not any exercise will do. The traumatic ones inducing muscle soreness are the most effective. It is the factors inducing soreness which will trigger this increase in insulinase.
On the other hand, you do not want to create too much soreness as it will temporarily reduce the effects of insulin and androgens by impairing their effects at the level of their respective receptors. What you want is mild but frequent soreness along with some very frequent pumping sessions.
OK, can anyone with any serious weight training knowledge take this paragraph seriously? We all know soreness is NOT an indication of muscle growth. This paragraph again makes me wonder about this author.
Do not forget both androgens and insulin circulate in the blood. The more blood you get into the muscles (and the longer it stays), the more your muscles will be "drenched" in those two hormones. Please note that insulinase is produced locally in the trained muscles only. It does not circulate into the blood.
Ok, that’s it.
