Insulin Resistance

We think of diabetes as a lack of insulin.  The strange thing, however, about the pre-diabetic state is that it is almost always associated with increased levels of insulin. Since insulin’s job is to get sugar out of the blood, the fact that there is an increased amount of insulin, but blood sugar levels remain higher than normal, means insulin is not succeeding in its job. This is what we mean by insulin resistance.

Luckily for us, our insulin resistance (or if you like – our insulin sensitivity) can change. This is where the importance of understanding insulin resistance comes in. If we can understand why people lose the ability to respond to insulin then we can find ways to regain insulin sensitivity.

To understand insulin resistance we need to understand what insulin does, and to understand what insulin does we need to know a bit about metabolism.

Metabolism involves the chemical conversion of all sorts of fuel molecules into different forms. Some forms are for storage, others are for generating power, others still are precursors for making yet other molecules. Now if we think of this as a big factory, we can imagine these molecules as moving along an assembly line. The “workers” in this assembly line are things called enzymes. Each enzyme performs one chemical reaction transforming a metabolic intermediate into the next intermediate on its way towards usage or storage.

Like our image of a global “just in time” supply chain, the metabolic factory can change its production goals at a moments notice. Certain enzymes can be modified to work slower or faster or stop work entirely. New enzymes can show up and send the molecular assembly line into a totally new direction. This is how the body regulates metabolism. Hormones like insulin supply the initial message to the metabolic factory giving it its new instructions.

Our understanding of insulin resistance involves understanding how that message gets to the factory floor. Insulin cannot simply enter the cell to give its message. Instead it binds to a protein sticking out of the cell called the insulin receptor. When insulin binds to its receptor it initiates a process inside the cell called “signal transduction” in which the signal is passed from protein to protein until it finally gets to the factory floor.

This brings us to the complexity of insulin resistance. The proteins that carry the insulin signal also carry other signals derived from other receptors such that the cell integrates all of its information before it hits that factory floor. A slowdown anywhere along the information chain can result in the message getting diluted or lost. Looking for that change in diabetes patients has been a long and arduous task. It seems that our varied genetics makes each of us vulnerable to loosing that insulin signal in a different way. One of the major goals of researchers is to try to find some unifying change that can link all of these different results into a common mechanism.

While we do not yet have a complete understanding of how insulin resistance works, we do have an exciting and completely natural therapy which can modify insulin sensitivity. It is called exercise. I’ll go over the data and some of the reasoning why it works in another post. Thus is our medical edifice dwarfed by a simple change in behavior.

Robert Scheinman

Robert Scheinman received a PhD in Pharmacology in 1990 and joined the faculty of the University of Colorado Denver School of Pharmacy in 1995. Robert runs a medical research laboratory focused on the role of inflammation in various disease states including diabetes, arthritis, and cancer.

Robert Scheinman

Robert Scheinman received a PhD in Pharmacology in 1990 and joined the faculty of the University of Colorado Denver School of Pharmacy in 1995. Robert runs a medical research laboratory focused on the role of inflammation in various disease states including diabetes, arthritis, and cancer.