Diabetes Still Isn't Easy
Diabetes Still Isn't Easy

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The Story of Insulin

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In my first blog post I spoke of humans being glucocentric, and pointed out that glucose doesn’t get to work unless insulin is present to get it into the cells (except the brain). From an evolutionary point of view, insulin is a very old molecule—we can tell because our insulin receptors (the part of our body cells that respond to insulin) sit on the boundaries of cells. In other words, half of the receptor is outside the cell and half inside.

Insulin and Cellular Communication

When insulin floats around in the blood stream and reaches a cell, it will attach to the outside part of the receptor like a key in a lock. That sets off a trigger on the inside of the cell that tells the cell to bring in glucose and metabolize it to release the energy contained within the glucose molecules. Imagine if the CEO of a company had to give an order to someone 10 floors below—but all the phones, computers, etc. are not working. So the message has to go down floor by floor. That’s what the insulin-cell messaging is like. In the cell, the message is sent down the “floors” by a series of proteins. It’s important to understand this process on some level, because when things go wrong, it is usually here that they do.

Insulin Production

Insulin is produced in the beta cells of “the Islets of Langerhans.” The islets also contain the alpha cells that produce another hormone—glucagon—that acts in opposition to insulin. Glucagon makes the glucose levels rise in the blood stream. About one million islets are scattered through out the pancreas.

Similar to many other proteins, insulin is derived from a larger protein called proinsulin—insulin is basically proinsulin with a piece (c-peptide) chopped off. Your current blood glucose levels determine how much insulin is produced. In fact, insulin is released almost by the minute in reaction to the changing blood glucose levels.  During starvation, the liver produces small amounts of glucose and in parallel, the beta cells put out virtually undetectable levels of insulin to maintain a status quo. If you starve too long your body runs out of building blocks to make glucose and blood sugar levels drop.

Insulin and Type 2 Diabetes

Now let’s look at the system and how a glitch results in type 2 diabetes.

First, the beta cell needs to have an abnormality that prevents it from secreting unlimited amounts of insulin. This may take many years to show itself. Second, there needs to be an insulin-receptor malfunction. To continue the metaphor, the key goes in the lock but it won’t turn—or the key goes in the lock and it turns but the tumblers are broken. This is called insulin resistance.

At first, things stay functional. As long as the beta cell keeps pumping out insulin, glucose stays in the normal range but sooner or later (10 years or 30 years), the beta cells can no longer keep up and glucose levels rise—this is type 2 diabetes. 

In the next blog we will dissect out what this means and what high insulin levels may do outside of the glucose story.

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About the Author


MD, FACP

Dr. Bernstein is director of the diabetes management program at the Friedman Diabetes Institute.

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