insulin resistance: confusion

[mikeynov]

reading a recent article on low carb benefits in misc.fitness.weights, lyle mcdonald made a variety of comments that have me somewhat confused.
i understand how insulin resistance develops, but i'm curious about its implications for fat retention and such. lyle is saying that insulin resistance appears to be an adaptation PREVENTING weight gain. he also says that insulin resistant people may respond more effectively to hypocaloric diets.

if the above are both true, why are there so many insulin resistant fatties running around? even if insulin resistance somehow creates perturbations in satiety, ie triggers people to overeat, this seems counterintuitive to its purpose of preventing weight gain, according to lyle's proposed model.
i'm curious how insulin resistance develops into a vicious cycle that leads to obesity, if it's the body's way of adapting AWAY from weight gain. perhaps i'm not reading his interpretations correctly...

i'd paste this stuff directly, but i shy away from doing such things without an author's permission. i can link the the post on misc.fitness.weights...

 

[Dianabol]

Dear mikeynov,

1. "lyle is saying that insulin resistance appears to be an adaptation PREVENTING weight gain. he also says that insulin resistant people may respond more effectively to hypocaloric diets."

In general, eventual downregulation of receptors responsiveness to hormones will occur. This is owing to over-stimulation by that hormone. Hormones have a half-life and their eventual degradation is enough to stop their hormonal signal from stimulating their respective receptors. The stoppage of the hormonal message is something natural - a cell cannot be doing one thing all the time and thus, for a moment, it "listens" to insulin, and then at another time, it responds to GH, glucagon Adrenalin and so on.

Thus, the eventual degradation of a hormone is part and parcel of a natural stoppage of the hormonal message.

If hormone levels remain unduly elevated and prolonged, the cells actually turn a deaf ear (i.e. become resistant to the hormone), so to speak, to the particular hormone. This is the second way of stopping the hormonal message so that the cell can respond to other hormones and do other things.

Thus, more of the same hormone is needed to further "nag" the cell into compliance when hormone resistance occurs. Such hormone resistance is particularly evident in insulin and testosterone.

Looking at insulin resistance in isolation, cells that become insulin resistant is perhaps, an adaptation - turning a deaf ear when the nagging becomes intolerable. This is the immediate, isolated response. But the body works in a systemic fashion, and isolated responses do not tell the whole story. What spillover effects occur from cellular insulin resistance?

In the case of insulin, insulin resistance occurs at skeletal muscle and liver cells but not adipose tissue. Humans have been adapted to storing fat as a safeguard against starvation. Storage of fat knows no limits, and is a survival adaptation. How can insulin resistance prevention weight gain?... perhaps, this occurs in the muscle and liver cells and possibly, fat cells. If a cell does not obey the instruction of insulin e.g. Type 1 Diabetes, then a person will literally starve at cellular level. This is perhaps, a parallel scenario of the initial adaptation Lyle must be referring to in terms of insulin resistance preventing weight gain. But again, we are adapted to unlimited storage of fat as a means of survival during starvation and this is perhaps, a subsequent adaptation to hyperinsulinemia.

2. "i'm curious how insulin resistance develops into a vicious cycle that leads to obesity, if it's the body's way of adapting AWAY from weight gain. perhaps i'm not reading his interpretations correctly..."

Very briefly:

increase in blood glucose-----> insulin secretion-----> decrease in blood glucose.

Too much glucose-------> too much insulin------> cells become insulin resistant--------> more insulin being secreted (vicious cycle).

Muscle and liver cells become resistant, fat does not so one gets fat on thsi vicious cycle.

Perhaps, you should re-read Lyle's post again. I am sure he, or any of us would be happy to discuss any and all issues you might raise.

Godspeed, and happy HSTing

 

[micmic]

They don't call you Dianabol for nothing

 

[mikeynov]

Quote[/b] (Dianabol @ April 25 2003,2:49)]Dear mikeynov,
1. "lyle is saying that insulin resistance appears to be an adaptation PREVENTING weight gain. he also says that insulin resistant people may respond more effectively to hypocaloric diets."
In general, eventual downregulation of receptors responsiveness to hormones will occur. This is owing to over-stimulation by that hormone. Hormones have a half-life and their eventual degradation is enough to stop their hormonal signal from stimulating their respective receptors. The stoppage of the hormonal message is something natural - a cell cannot be doing one thing all the time and thus, for a moment, it "listens" to insulin, and then at another time, it responds to GH, glucagon Adrenalin and so on.
Thus, the eventual degradation of a hormone is part and parcel of a natural stoppage of the hormonal message.
If hormone levels remain unduly elevated and prolonged, the cells actually turn a deaf ear (i.e. become resistant to the hormone), so to speak, to the particular hormone. This is the second way of stopping the hormonal message so that the cell can respond to other hormones and do other things.
Thus, more of the same hormone is needed to further "nag" the cell into compliance when hormone resistance occurs. Such hormone resistance is particularly evident in insulin and testosterone.
Looking at insulin resistance in isolation, cells that become insulin resistant is perhaps, an adaptation - turning a deaf ear when the nagging becomes intolerable. This is the immediate, isolated response. But the body works in a systemic fashion, and isolated responses do not tell the whole story. What spillover effects occur from cellular insulin resistance?
In the case of insulin, insulin resistance occurs at skeletal muscle and liver cells but not adipose tissue. Humans have been adapted to storing fat as a safeguard against starvation. Storage of fat knows no limits, and is a survival adaptation. How can insulin resistance prevention weight gain?... perhaps, this occurs in the muscle and liver cells and possibly, fat cells. If a cell does not obey the instruction of insulin e.g. Type 1 Diabetes, then a person will literally starve at cellular level. This is perhaps, a parallel scenario of the initial adaptation Lyle must be referring to in terms of insulin resistance preventing weight gain. But again, we are adapted to unlimited storage of fat as a means of survival during starvation and this is perhaps, a subsequent adaptation to hyperinsulinemia.
2. "i'm curious how insulin resistance develops into a vicious cycle that leads to obesity, if it's the body's way of adapting AWAY from weight gain. perhaps i'm not reading his interpretations correctly..."
Very briefly:
increase in blood glucose-----> insulin secretion-----> decrease in blood glucose.
Too much glucose-------> too much insulin------> cells become insulin resistant--------> more insulin being secreted (vicious cycle).
Muscle and liver cells become resistant, fat does not so one gets fat on thsi vicious cycle.
Perhaps, you should re-read Lyle's post again. I am sure he, or any of us would be happy to discuss any and all issues you might raise.
Godspeed, and happy HSTing

i appreciate the long explanation you gave, but i understood the logic of insulin resistance before posting this

[blood glucose] > upper normal limit -> secretion of insulin from beta cells of pancreas

ie rapid elevation of blood glucose concentration yields a concomitant rapid increase in insulin to 'dispose' of this glucose into tissue cells. the cells themselves have a 'set point' of cellular receptivity to insulin, and chronic overstimulation causes them to 'turn a deaf ear' as you say, which in turns requires even more insulin secretion to dispose of a given concetration of blood glucose, and so the vicious cycle continues.

that's all fine and well, but the final thrust of your argument is that this occurs in skeletal muscle and liver tissue (with the former being the primary means of glucose disposal), but not adipose tissue. this was my understanding as well, but lyle's post seemed to indicate otherwise. did you actually read it?

as i said, i appreciate the physiology, bit i understood the vicious nature of the cycle. if we CAN conclude it affects primarily skeletal muscle (as was my understanding), and thus, calories are naturally shunted into adipose tissue, then it makes perfect sense. if not (and lyle refers to research that being insulin resistant helps one lose fat more quickly - explain), then i am confused...

do you see what i'm saying?

-michael

 

[mikeynov]

and, for reference, this is exactly what lyle said. if bryan or anyone would like me to remove this quote, just ask

'Interestingly, the research suggests the exact opposite: insulin
resistance DEVELOPS to try and prevent further weight gain. If you think
about what insulin resistance (esp. at the fat cell) means, this makes
sense. When you consider the hyperglycemic, hypertriglyceridemia and
all the rest that develops with IR, you realize something very simple:
with severe insulin resistance, you can NOT push calories into fat cells
(which is why they build up in the bloodstream), this PREVENTS further
weight gain.

As well, studies using controlled caloric intakes show no relationship
between insulin resistance and weight loss.

http://www.ncbi.nlm.nih.gov:80/entrez....0022419

For some pertinent studies. note that, in some studies, being insulin
resistant leads to GREATER weight losses.

The issue is that, with some diet interpretations (esp higher carb/lower
fat esp. when the carbs are high on the glycemic index), insulin
resistance folks have trouble controlling calories and end up eating
more. It's the eating more that causes the weight gain. The insulin
resistance is a precipitating factor, of course, but it's not the causal issue.'

 

[Aaron_F]

I see one small problem in what lyle wrote PREVENTS
IT doesnt prevent, it will lower the potential weight gain.
IR resutls from lack of physical activity (reducing muscular insulin sensitivity) and increases in visceral adipose mass, which increases the release of adipose dirived 'hormones' leptin adn IL6 (the adipose also releases other ILs and TNFs but these dont seem to provide much to the overall picture) Both these hormones reduce insulin sensivity in the fat cell. Which is why fat loss will generally result in quite a significant increase in insulin sensitivity (body making a reaction to a change in calories at a local level).
Insulin resistance is the bodies reaction ot gaining fat (and reducign activity) to try and minimise weight gain. But obviously it was never meant to react to such an increase in bodyweight and excess food, and therefore it is ineffeficient to manage current situations. THerefore overall it will lead to diabetes

 

[micmic]

Things are complicated, but the essence won't change. It's true that bigger adipocytes will become more insulin resistant (resistin and GLUT4 seem to play an important role), but they have to get bigger in order to become IR... Not only that, but also basal (not insulin dependent) glucose uptake is reduced in obese individuals. But what we already know still applies:

1. Obese people are more insulin resistant
2. Obese people lose more easily bodyfat

Here's a study that shows how complex things can be:
Glucose uptake and insulin action in human adipose tissue

 

[mikeynov]

hehe, for all you guys are saying, just answer this one question. as i've said, i understand the physiology, even at the cellular level.

muscle is the primary means of glucose disposal in the bloodstream, which makes infinite sense, as muscle tissue carries the highest demand for glucose to move our lazy asses around.

i would think that muscle would be the most affected in a state where hyperinsulinemia is occurring (condition of excess secretion of insulin in the blood). ie a desparity between muscle tissue's response to these conditions and adipose tissue.

thus calories get partitioned away from muscle and, even if adipose tissue becomes resistant to the effects of insulin, not as much as muscle tissue, into adipose tissue. we're playing a partitioning game where muscle gets crappy at disposing of glucose, adipose tissue starts footing the bill a bit, and eventually you have high blood levels of triglycerides, etc etc.

this is all fine and well.

my question: DOES muscle tissue respond more severely to hyperinsulinemic events than adipose tissue? ie if both become insulin resistance concomitantly, i'm not sure why calories would be partitioned in the direction of adipose tissue. which sounded, to me, kind of like what lyle was saying.

 

[micmic]

Quote[/b] ]my question: DOES muscle tissue respond more severely to hyperinsulinemic events than adipose tissue? ie if both become insulin resistance concomitantly, i'm not sure why calories would be partitioned in the direction of adipose tissue.

Either way the result would be increased total fat even if it is intramuscular:

Increased efficiency of fatty acid uptake contributes to lipid accumulation in skeletal muscle of high fat-fed insulin-resistant rats
Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides

 

[Dianabol]

"my question: DOES muscle tissue respond more severely to hyperinsulinemic events than adipose tissue? ie if both become insulin resistance concomitantly, i'm not sure why calories would be partitioned in the direction of adipose tissue. which sounded, to me, kind of like what lyle was saying."

If insulin receptors on muscle and liver but not adipose tissue become insulin resistant, the individual would get very fat and starve to death. Insulin resistance in adipose tissue would have the opposite effect in that the fat cells get starved while the muscle and liver cells get amply fed. Insulin resistance in adipose tissue only will have an indirect nutrient partitioning effect simply because adipose tissue is not receptive to insulin and thus nutrients cannot be stored in adipose tissue as fat but has to go to muscle and liver and if those tissues in turn, have taken all the nutrients they need, then there will be a build-up of nutrients in the bloodstream. This is perhaps, bad, especially if you consider it in a hyperglcaemic sense. Amino acids and lipids should not build up in the bloodstream assuming normal liver deamination and proper functioning of other means of non-insulin dependent fat-disposal mechanisms.

All else being equal, muscle does not respond differently from adipose tissue when activated by insulin but its extent of responsiveness is modulated via two main factors. 1) Finite storage space: Storage of muscle glycogen is finite and if muscle glycogen is full, GLUT 4 transporters are not going to respond to insulin and store glucose as glycogen simply because there is no space. 2) Number of receptors: Furthermore, because of the sheer number of insulin receptors to be found on adipose tissue, the lion's share of glucose tends to be taken up by adipose cells.

Thus, the relative insulin resistance is perhaps, second place to the absolute insulin resistance, which, in muscle and liver cells limits the amount of nutrient uptake while in adipose tissue, such a situation is modulated by a vast increase in number of insulin receptors and unlimited storage space. These are some reasons why the use of insulin injections is contraindicative for Type II NIDDM.

The best thing that can happen is for fat cells to become insulin resistant while there is a simultaneous increase in sensitivity to insulin by muscle and liver cells. To date, no drug of this sort exists. But, this can occur with exercise - exercise actually activates GLUT 4 transporters on muscle cells sans insulin. This is why regular exercise is recommended as a superior means of maintaining blood sugar health.

When Lyle said that insulin resistance prevented weight gain, then it must be in the context of a particular tissuel type (e.g. muscle, liver or fat) not responding and thus, starving.

When total insulin resistance is taken into account, it is realized that adipose tissue exhibits the least insulin resistance relative to other tissue types for reasons mentioned above and thus, becomes the primary depot for nutrient storage.

 

[mikeynov]

Quote[/b] (Dianabol @ April 27 2003,4:29)]"my question: DOES muscle tissue respond more severely to hyperinsulinemic events than adipose tissue? ie if both become insulin resistance concomitantly, i'm not sure why calories would be partitioned in the direction of adipose tissue. which sounded, to me, kind of like what lyle was saying."
If insulin receptors on muscle and liver but not adipose tissue become insulin resistant, the individual would get very fat and starve to death. Insulin resistance in adipose tissue would have the opposite effect in that the fat cells get starved while the muscle and liver cells get amply fed. Insulin resistance in adipose tissue only will have an indirect nutrient partitioning effect simply because adipose tissue is not receptive to insulin and thus nutrients cannot be stored in adipose tissue as fat but has to go to muscle and liver and if those tissues in turn, have taken all the nutrients they need, then there will be a build-up of nutrients in the bloodstream. This is perhaps, bad, especially if you consider it in a hyperglcaemic sense. Amino acids and lipids should not build up in the bloodstream assuming normal liver deamination and proper functioning of other means of non-insulin dependent fat-disposal mechanisms.
All else being equal, muscle does not respond differently from adipose tissue when activated by insulin but its extent of responsiveness is modulated via two main factors. 1) Finite storage space: Storage of muscle glycogen is finite and if muscle glycogen is full, GLUT 4 transporters are not going to respond to insulin and store glucose as glycogen simply because there is no space. 2) Number of receptors: Furthermore, because of the sheer number of insulin receptors to be found on adipose tissue, the lion's share of glucose tends to be taken up by adipose cells.
Thus, the relative insulin resistance is perhaps, second place to the absolute insulin resistance, which, in muscle and liver cells limits the amount of nutrient uptake while in adipose tissue, such a situation is modulated by a vast increase in number of insulin receptors and unlimited storage space. These are some reasons why the use of insulin injections is contraindicative for Type II NIDDM.
The best thing that can happen is for fat cells to become insulin resistant while there is a simultaneous increase in sensitivity to insulin by muscle and liver cells. To date, no drug of this sort exists. But, this can occur with exercise - exercise actually activates GLUT 4 transporters on muscle cells sans insulin. This is why regular exercise is recommended as a superior means of maintaining blood sugar health.
When Lyle said that insulin resistance prevented weight gain, then it must be in the context of a particular tissuel type (e.g. muscle, liver or fat) not responding and thus, starving.
When total insulin resistance is taken into account, it is realized that adipose tissue exhibits the least insulin resistance relative to other tissue types for reasons mentioned above and thus, becomes the primary depot for nutrient storage.

thank you dianabol...and very good stuff YOU'RE MY NEW BUDDY

 

[Dianabol]

The pleasure is mine, only too glad to compare notes.

Godspeed, and happy HSTing

 

[virtualcyber]

Quote[/b] (mikeynov @ April 24 2003,11:53)]reading a recent article on low carb benefits in misc.fitness.weights, lyle mcdonald made a variety of comments that have me somewhat confused.
i understand how insulin resistance develops, but i'm curious about its implications for fat retention and such. lyle is saying that insulin resistance appears to be an adaptation PREVENTING weight gain. he also says that insulin resistant people may respond more effectively to hypocaloric diets.
if the above are both true, why are there so many insulin resistant fatties running around? even if insulin resistance somehow creates perturbations in satiety, ie triggers people to overeat, this seems counterintuitive to its purpose of preventing weight gain, according to lyle's proposed model.
i'm curious how insulin resistance develops into a vicious cycle that leads to obesity, if it's the body's way of adapting AWAY from weight gain. perhaps i'm not reading his interpretations correctly...
i'd paste this stuff directly, but i shy away from doing such things without an author's permission. i can link the the post on misc.fitness.weights...

Basically Lyle is saying this: when a person becomes obese, his body makes an ill-fated attempt to not become any more fat by developing insulin resistance.

This is why insulin resistance and obesity tend to go together.