Toward an understanding of insulin resistance

The body's regulation of insulin and glucose are involved in three related diseases: types 1 and 2 diabetes and metabolic syndrome. Insulin resistance is considered to be a pathological condition that causes type 2 diabetes and metabolic syndrome; insulin resistance is not involved in type 1 diabetes.

Insulin is a hormone that enables glucose, which is the body's primary source of energy, to pass from the bloodstream into each cell through a protein structure in its wall called an insulin receptor. If the supply of insulin is inadequate, as in type 1 diabetes, glucose cannot pass through the receptor into the cell. And even if the supply of insulin is adequate, its action on receptors can be prevented by insulin resistance, as in type 2 diabetes and metabolic syndrome.

Type 1 diabetes is characterized by very high levels of blood sugar (serum glucose), which can be reduced successfully by regular injections of insulin.

Type 2 diabetes is also characterized by high levels of blood sugar, which can be reduced successfully by regular injections of insulin or, less successfully, by the regular use of pharmaceutical drugs; insulin injections are inconvenient and potentially dangerous.

Metabolic syndrome, which was discovered recently by Stanford endocrinologist Gerald Reaven, is characterized by slightly elevated levels of blood sugar and very high levels of blood insulin.

According to Dr. Reaven, some individuals are capable of overcoming insulin resistance by producing prodigious quantities of insulin, which avoids type 2 diabetes but results in metabolic syndrome. Individuals who cannot overcome insulin resistance by producing large quantities of insulin merely have type 2 diabetes. Both metabolic syndrome and type 2 diabetes are serious diseases, and it is believed that metabolic syndrome may eventually evolve into type 2 diabetes if the pancreas loses its capacity to produce abnormally large quantities of insulin.

We come at last to the nature of insulin resistance, which is considered to be the cause of either the dangerously high levels of blood sugar (hyperglycemia) in type 2 diabetes or else of the dangerously high levels of compensatory insulin (compensatory hyperinsulinemia) in metabolic syndrome. Insulin resistance is considered to be a defect in the insulin receptor or in the insulin itself. The thinking is as follows: insulin must work with insulin receptors in order for glucose to pass from the bloodstream into the cells, thereby reducing blood sugar levels to normal. I believe this thinking is wrong.

It is known now that insulin receptors are only present in the cells of certain kinds of tissue (e.g., muscle and fat), while the cells of other tissues (e.g., the kidneys, red blood cells, and -- most notably -- the brain) allow glucose to enter through their walls freely without any need for insulin receptors or insulin.

Suddenly the picture changes completely. Glucose can enter cells freely without the 'help' of insulin! Of what use, then, is the insulin/insulin receptor mechanism, which is what makes insulin resistance possible? It becomes obvious that this mechanism is actually designed to permit insulin resistance to occur. Therefore, insulin resistance, per se, must be normal, not pathological.

If insulin resistance is normal, then what purpose could it serve? Without insulin receptors, all cells in the body would have to allow glucose to enter their cells freely. Every organ in the body -- including the brain -- would receive the same amount of glucose. But the brain, which uses 25% of the body's glucose supply, cannot function without enough glucose; we know that severe hypoglycemia can cause coma and death.

During starvation, the supply of glucose is so diminished that the body begins to metabolize its own protein to survive. More glucose can be preserved in the bloodstream by insulin resistance, which prevents glucose from being 'wasted' on nonessential tissues such as skeletal muscle and fat. And the body can only survive as long as there is an adequate supply of blood sugar for the brain.

In short, I believe that insulin resistance is a natural survival mechanism designed to preserve life by preventing serum hypoglycemia.

Eugene Paul