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EricT · 07-12-2006, 08:59 AM

I haven't seen Part 2 of this article anywhere.

Insensitivity, Part I
By Lyle McDonald

Depending on what types of things you like to read, you've probably seen it stated that insulin resistance makes you fat, makes it impossible to lose weight, or something along those lines. Supplement companies often put insulin sensitizers such as vanadyl or alpha-lipoic acid into their fat burners and everybody wants to improve insulin sensitivity.

As usual, I'm here to rain on your parade and explain the realities of insulin resistance; this will probably mean that I'll shatter some of your preconceived notions. And, while I'm exceptionally lazy and am not going to fully reference this article, I'm going to provide you with enough references to get started and go see if what I say is correct or not.

In this part of the article, I mainly want to cover the physiological basics of insulin, its roles in the body, and some fundamental concepts of insulin resistance. In Part II, I'll explain how insulin resistance develops, what it actually means in terms of weight/fat gain or loss, and how to best harness insulin resistance or sensitivity for different goals.

What is insulin?

Although I wish I could assume that all readers of my articles have the basics down, I often find that this isn't the case. As such, here's a primer on the hormone insulin.

Insulin is a peptide (protein-based) hormone released from the pancreas in response (primarily) to increasing blood glucose levels, meaning that dietary carbohydrates have the greatest impact on insulin levels. However, it's important to know that protein can also raise insulin. Dietary fat doesn't raise insulin per se but can, through other indirect mechanisms, affect insulin levels in the body (mainly by altering insulin sensitivity or resistance).

What does insulin do?

In the simplest of terms, insulin is a storage hormone. When levels go up, the body "knows" that it has nutrients and should adapt accordingly. In doing so, it affects most tissues of the body (it also sends signals to the brain), but I'm going to only talk about three, and focus on only two.

In the liver, for example, an increase in insulin levels decreases the liver's release of glucose and stimulates glycogen storage (said glycogen being used later to maintain blood glucose levels). I won't really talk much more about the liver in this article.

In muscle cells, insulin increases glucose uptake, storage, and oxidation. It also increases amino acid transport into the muscle and inhibits protein breakdown; this has a net effect of increasing the protein content of muscles. Insulin probably also affects intramuscular triglyceride (IMTG) levels in muscle cells.

In fat cells, insulin increases glucose uptake and activates an enzyme called lipoprotein lipase (LPL). LPL is responsible for mobilizing fatty acids from circulating chylomicrons (from dietary fat), but a different enzyme, acylation stimulation protein (ASP), appears to be more important for the actual fat storage in the fat cell. In all honesty, an entire article could and should be written about the confusion over LPL and ASP. Additionally, insulin inhibits the enzyme hormone stimulated lipase (HSL), which breaks down stored triglycerides so that they can be released into the bloodstream and burned for energy elsewhere (liver and muscle primarily). So, the net effect of insulin on fat cells is to increase fat and glucose storage and inhibit fat breakdown.

Like I said, insulin is basically a storage hormone, increasing the storage of nutrients (and inhibiting their release/breakdown) in liver, muscle and fat cells.

How hormones work: a simple overview

All hormones in the body work by binding to specific receptors. When binding occurs, depending on a few other specifics, stuff happens. I'll demonstrate this using the extremely technical graphic (converted to ASCII, which sucks) that I used in my second book "Bromocriptine."

Figure 1: Mechanism of hormone action

Hormone -----> Binds to Receptor -----> Makes Stuff happen

Note that there are a multitude of steps between the receptor and stuff happening phases, but they aren't really critical to this article or the average trainee or reader.

So in the case of insulin, there is a specific insulin receptor and, when insulin binds to it, the aforementioned physiological effects take place. What determines how much of the stuff happens? Simply speaking, two things: hormone levels and receptor sensitivity (or resistance, which is just the opposite of sensitivity).

Now, the levels of insulin are going to be predominantly determined by diet; high carbs and protein will lead to higher insulin levels than lower carbs or protein. Also, the level of insulin sensitivity or resistance will affect how much of a hormone the body is going to release, so let's look at that issue specifically.

What is insulin sensitivity/resistance?

In simple terms, receptors vary in how sensitive they are to a hormone. This is true for all hormones and their receptors, including insulin. So, for a given level of hormone, you see different levels of stuff happening. If the receptor is highly sensitive, a small amount of hormone will have a large effect (lots of stuff happens). If the receptor isn't sensitive (it is resistant), a large amount of hormone will have little effect (not much stuff happens). In the latter scenario, even if there is a high level of the hormone in circulation, there is still less stuff happening.

If this is confusing, consider the following poorly chosen example. Imagine you have a stereo that is sending out a certain strength signal; this is analogous to insulin levels. The sound that comes out of the speakers is the stuff that happens. Now imagine what happens if you use cheap, shitty cords (meaning high signal resistance) to hook the stereo to the speakers; for any given level of output from the stereo, the sound output will be low. Now, imagine you use monster, low resistance cables; the sound output goes up.

In the first example, either you accept low volume output, or you crank up the volume knob of the speaker (equivalent to increasing insulin levels) to try and get more volume out of the speakers.

What causes insulin resistance?

Since the discovery of the Metabolic Syndrome, the mechanisms behind insulin resistance have been a major area of study. Unfortunately, there is no single cause of insulin resistance, but we can look at a few of the major ones. Note that these different effects occur at different time frames. Some have effects over a few hours or a few days, and some take weeks or even months to occur.

One cause is insulin levels themselves. When a tissue is exposed to chronically high levels of insulin (i.e. because someone was eating too many refined carbohydrates every day), it will tend to decrease insulin sensitivity; when insulin levels drop, insulin sensitivity goes up. Note that this is a process that occurs over many days; it's not immediate. I bring this up because of some recent suggestions to avoid high glycemic (high insulin producing) carbs post-workout, based on the idea that it will somehow cause insulin resistance. Simply put, a single spike of insulin is not going to cause insulin resistance or receptor downregulation. Rather, it takes chronically high insulin levels caused by a chronically high intake of highly refined carbohydrates to get these unfavorable effects.

Secondly, when tissues (and this includes liver, muscle and fat cells) become '"full" of nutrients, they tend to become insulin resistant. Recall that insulin is a storage hormone; therefore, this makes good sense. If a cell is full of nutrients, there's no way (or reason) to store more, so that tissue becomes resistant. This has a couple of implications that I'll discuss in the next part of this article.

On a related note, both fat and glycogen storage within tissues (liver and muscle) cause insulin resistance to occur. So when you're overeating either carbs or fat, you can make a tissue insulin resistant. I bring this up since it's common for authors to blame one or the other; the point is that both contribute. Keep in mind that activity also interacts with this. When you regularly deplete tissues of nutrients (i.e. exercise, you lazy sack), they become more insulin sensitive. This facilitates nutrient storage when they become available again (i.e. this is a big part of why nutrients after a workout are shuttled preferentially into muscle; increased insulin sensitivity and nutrient storage exerts a partitioning effect).

There are many other contributors to insulin resistance. One is blood free fatty acid levels; when they are increased (because insulin goes down, for example), tissues tend to become insulin resistant. This also makes good sense, as there's no reason for the body to take up glucose when it already has plenty of fat to use for fuel. This ends up having a beneficial effect on adaptation that I'll cover in the next section.

There is some evidence that even high fat meals can cause insulin resistance on a meal-to-meal basis. Additionally, dietary fat has other, longer-term (months) effects on insulin resistance by physically altering cell membrane structure. Saturated fats will tend to decrease insulin sensitivity (increase resistance), while monounsaturated and polyunsaturated fats will improve insulin sensitivity. Again, this is a process taking many months to occur; just switching fat sources on a meal-to-meal or day-to-day basis won't have much of an effect.

I mentioned above that activity improves insulin sensitivity by depleting cellular energy stores, but this isn't complete. Severe muscle damage (from heavy eccentrics) can actually cause insulin resistance, most likely by physically damaging the cell membrane, leaving the insulin receptor with no place to bind. Whether this applies to all but the most intensive types of training programs is up to debate; most studies use insane levels of eccentric trauma (some absurd number of maximal eccentric contractions or downhill running) to generate the effect. Regardless, it's something of which you out to be aware.

Summary of Part I

So that's a basic overview of the hormone insulin and insulin resistance. The main factors to take from this article are that

a) Insulin is a storage hormone; it stimulates glycogen storage in liver, glycogen, protein and fat storage in muscles and glucose and fat storage in fat cells. It also decreases fat mobilization from fat cells and glucose output from fat cells.
b) Insulin resistance refers to a situation where the insulin receptor no longer responds to the signal that insulin is supposed to send.
c) There are a number of factors - both acute and long-term, and dietary and activity- that affect insulin sensitivity/resistance.