What is insulin resistance, why does it occur, and why is it typically associated with high insulin levels?

Insulin has a prominent hormonal effect on skeletal muscle fibers, liver cells, and fat cells; in these tissues, it encourages uptake and discourages the release of blood sugar (glucose) and fats.  In other words, insulin promotes fuel storage. Insulin resistance refers to a condition in which these tissues respond inefficiently to the insulin signal, so that higher levels of insulin are required to get its metabolic job done properly.  Insulin resistance is usually compensated by increased insulin release by the pancreas, which leads to elevated blood levels of insulin all day long; that’s why combating insulin resistance is crucial to a low-insulin lifestyle.  Insulin resistance of muscle, liver and fat cells is typically seen in a common metabolic disorder known as “metabolic syndrome”, which is usually associated with and caused by an excessive accumulation of fat in the body’s abdominal regions.  People with metabolic syndrome are at increased risk for heart disease, stroke, dementia, diabetes, and many types of cancer.

Insulin resistance typically develops in people who have an excess of fat tissue – particularly fat tissue in the abdominal region.  The overstuffed fat cells in abdominal fat become inflamed, and as a consequence of this, they become less sensitive to insulin.  As a result, these fat cells tend to release fatty acids at times when they aren’t needed as a source of metabolic fuel.  This released fat, instead of being burned for fuel, can accumulate in other tissues, such as skeletal muscle fibers and liver cells.  And this misplaced fat can be converted to certain compounds that act to impair the intracellular signaling mechanisms triggered by insulin, making it hard for insulin to do its job.  In other words, skeletal muscle and the liver become insulin resistant too. 

The body has a clever way of coping with this problem.  The excessive amounts of fat released by insulin resistant fat cells act on the insulin-producing beta cells of the pancreas to “up-regulate” their production of insulin, so that, at any given blood sugar level, they make more insulin.  Because of this, people who are insulin resistant often manage to keep their blood sugar under reasonable control, and the release of fatty acids by fat cells is reined in to a degree.  But this comes at the cost of continual, round-the-clock elevations of blood insulin levels – hyperinsulinemia.  The implication of this is that certain insulin-responsive tissues that don’t become insulin resistant, are exposed to a continual excess of insulin activity.  This excess tends to drive the aging process, inhibit protective autophagy, promote oxidative stress, and boost cancer risk.   And the fatty acid excess associated with this syndrome – known as “metabolic syndrome” – also promotes oxidative stress and contributes to risk for vascular disease and other health disorders by inducing pro-inflammatory effects.

Fat cells make certain circulating hormones known as “adipokines” – leptin and adiponectin are key examples – that modulate the function of many tissues.  When fat cells become unduly enlarged in overweight people, this disrupts the production of these hormones; inadequate amounts of protective adiponectin are made, whereas excessive amounts of others, such as leptin, are produced.  Overstuffed fat cells are tend to make increased amounts of pro-inflammatory hormones – such in interleukin-6 and tumor necrosis factor-alpha – which can promote inflammation in the body’s tissues.  These perturbations of hormone production by fat cells are believed to contribute to the pathogenic impact of abdominal obesity and metabolic syndrome.

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