the thing to realize is what insulin resistance actually implies. Insulin is a storage hormone, stimulating nutrient uptake in many tissues (including liver, muscle, and fat cells). This is especially true for glucose.
So what happens when fat cells are insulin resistant? It means that insulin can't inhibit lipolysis (fat breakdown). Nor can it activate nutrient storage. This is part of why severely insulin resistannt individuals get increased blood levels of glucose, fatty acids and cholesterol, insulin is unable to either limit release from the cell or stimulate uptake. Since muscle is full (see below), they either get stored in inappropriate places (beta-cells of the liver) or float around in the bloodstream.
What about in muscle? An insulin resistant muscle cell is unable to uptake glucose. Without glucose to use for fuel, the cell has to find an alternative source. In this case, that alternative source is fatty acids.
So when fat cell insulin resistance is high, fatty acids are easier to mobilze. When muscle cell insulin resistance is high, glucose isn't used for fuel and fatty acids are. So in a caloric deficit, this means you use more fat for fuel b/c they are coming out of fat cells more easily and muscle is usingg them preferentially for fuel.
this is part of how things like clen, EC and GH work. By mobilizing fatty acids at a high rate and making the muscle cell insulin resistant, muscle has to forego glucose for fuel and use the mobilized fatty acids instead (note: this also spares protein in a carb insufficient state). A recent study on GH found that the fatty acid mobilizing effect of GH was THE key to its protein sparing effects: block the increase in fatty acids and you get the same amount of protein loss.
On that note, you should realize that studies examining predisoposition to obesity (for example, in the Pima indians) find that insulin sensitivity predicts weight gain and insulin resistance predicts weight loss or stability.
Insulin resistance develops with obesity and can be thought of as a way for the body trying to prevent further weight gain. Note that this is different in growing individuals such as children or pregnant women.
To be even more accurate to what I wrote above you need to differentiate muscle insulin resistance from whole body insulin resistance. In general, the body will develop insulin resistance in this order:
liver then muscle then fat cell
There are some weird genetic exceptions but the above would be a typical progression with diet induced insulin resistance.
Now, when muscle becomes insulin resistant, this shuttles more calories to the fat cells preferentially. In that sense, localized (muscular) insulin resistance causes more fat to be gained for a given caloric load. It's negative calorie partitioning. Note that this isn't only local, there are central (brain effects) controlling these processes as well.
This makes perfect sense: if the muscle is plenty full of nutrients and there is still a surplus, they should get pushed into storage as effectively as possible. So the msucle stops accepting nutrients and the rest go to the fat cells. The best way to prevent this is not to overeat and to deplete muscular fuel stores with exercise. In modern society, we do both: eat too much and don't exercise often enough. So muscle gets full of nutrients, becomes insulin resistant, and the excess calroeis go to fat cells post haste.
But as fat cells get filled up, problems start. The fat cell starts releasing a lot of hormones such as leptin, TNf-alpha, resistin (may only be relevant in rats) and others that prevent further nutrient storage (you can also get an increase in fat cell number). Now you're developing full body insulin resistance.
Once full body insulin resistance develops (with obesity), this acts to LIMIT further weight gain. Note that insulin resistance also means higher basal levels of insulin (there are also higher levlels of leptin as you get this fat). Both insulin and leptin *should* act to signal the brain to make you stop eating but the system isn't very sensitive to that. Additionally, it serves to push nutrients towards oxidation when you diet for the reasons above.
It's interesting to note that individuals without fat cells (lipodystrophy), which mimicks full body insulin resistance are protected against weight gain. First their muscles and liver fill up with nutrients, then they develop severe hyperglycemia, hypercholesterolemia and all the rest. Individuals with severe genetic insulin resistance have the same effect occur: they don't gain weight. They get a bunch of other health problems if you overfeed them but the severe genetic insulin resistance makes it so tnutrients can't be stored in their cells.
Also consider that insulin sensitivity improves as you lose weight. And the single time you are most prone to gain wight is at the end of the diet: when you are most insulin SENSITIVE.
As above, insulin sensitivity predicts weight gain, insulin resistance (full body) weight/fat loss.
Basically insulin resistance isn't always BAD. Quite in fact, it can be adaptive.
Now, in the context of excess calories/carbs and no activity (i.e. weight gain), insulin resistance is a bad thing to have. If you have muscular insulin resistance, more calories go to fat cells. If you have ful lbody insulin resistance, excess calories either sit in the bloodsream or get stored in the wrong spots, causing cell death.
Actually, if the goal is muscle gain with limited fat gain, it'd be wonderful to have fat cells resistant to nutrient storage and locally increase muscular insulin sensitivity. This would cause preferential nutrient partitioning to muscle. The question is how to do it. I have an idea but it's not fully fleshed out. For fatter individuals who begin an exercise program, this occurs naturally which is (IMO) one reason they can lose fat and gain muscle at the same time. The exercise preferentially improves muscular insulin sensitivity, the fat cells are releasing fat like nobody's business and you get calorie partitioning until the point that it all starts to balance out.
When you're dieting and not eating enough carbs (by definition, on a diet, carbs are reduced), insulin resistance is adaptive. By making muscle rely on fatty acids for fuel, glucose is spared for the brain and other tissues which require it.
Note that most of the current insulin sensitizing medications (especially the TZD drugs) cause further weight gain. Obesity docs don't care becuse they just want to see blood glucose and the rest levels go down.
As above, whole body insulin resistance develops in an effort to both limit further fat/weight gain and ensure that the body burns the fat off (sparing muscle) when you diet. This would have been adaptive in the context of our evolutionary dieting pattern, it's maladptive in our current environment.
Right before his death, Dan Duchaine commented that adding insulin sensitizersr to a diet seemed to increase muscle loss.
Insulin Sensitivity vs. Insulin Resistance
Insulin Sensitivity vs. Insulin Resistance
Psalms 51:10-13
Descent read, thanks for posting.Originally Posted by rockstarsar
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