Learning About the Insulin Response

All most people know about insulin is that it has something to do with sugar and diabetes. Insulin is amazing and complicated, and I wanted to learn more about how it works.


Human insulin is a hormone composed of 51 amino acids. (How does God think of this stuff?) All animals make insulin, and these insulins are pretty similar. Thirty years ago, most insulin given to people came from pigs and cows. According to Wikipedia, even insulin from some species of fish can be clinically effective in humans.

What Does Insulin Do?
You probably know that insulin gets glucose into muscle (and several other types of) cells. It does that by coordinating at least four proteins that make a bridge for glucose to cross the cell membrane. This coordination is sometimes called “insulin signaling,” and when the other proteins don’t cooperate, that is called “insulin resistance.”

Insulin has more responsibilities. It helps move glucose into the liver for storage as a starch called glycogen. It brings glucose to fat cells to make new fat. It helps get amino acids into cells to create new proteins, and encourages DNA to replicate, so cells can reproduce.

Insulin also stops a lot of processes. It stops the liver from releasing glycogen back into the blood as glucose. It stops fat cells from releasing fatty acids for use as fuel. Because it helps build up fats and proteins, and keeps them from breaking down, insulin is called an “anabolic” (body-building) hormone.

There’s more to insulin’s work. It regulates body temperature, raising it after meals. It works in the brain to enhance learning and memory. Some people think that too-low levels of brain insulin are a main cause of Alzheimer disease. Insulin also relaxes arteries, allowing more blood to flow through.

How is Insulin Made?
Insulin is made in “beta cells” in the “islets of Langerhans,” little clusters of cells in the pancreas. (The word insulin comes from the Latin word for island.) Once made, insulin is stored in pouches called “vesicles.”

Beta cells are supposed to produce insulin 24/7. The body needs a little insulin at all times, to stop the liver from dumping glucose into the blood, stop fat from breaking down, and to bring glucose to tissues that have gotten low on fuel.

This constant low-level insulin is called “basal insulin.” If you don’t have it, your blood glucose levels will rise, especially during the night as glycogen is released from liver.

When new food comes into the bloodstream after eating, we need much more than basal insulin to process it. This is sometimes called “bolus insulin” and is released in two stages.

In a person without diabetes, insulin is released from the vesicles when the body detects the amino acids leucine and arginine, or the sugars glucose and mannose. Releasing stored insulin is called the phase 1 insulin response. It enables people without diabetes to eat chocolate cake and ice cream without having their glucose levels rise much. But people with diabetes usually have little or no stored insulin, which is why glucose spikes after meals.

It takes time to produce new insulin, called the “phase 2 response,” especially if you have diabetes. That’s why you want foods that take a long time to turn into glucose (have a low glycemic index.) Or you want to take fast-acting insulin to cover the spike.

What Goes Wrong?
Diabetes can interfere with insulin in several ways. In Type 1, something destroys the beta cells. The usual culprit is thought to be the immune system’s mistaking beta cells for a threat and attacking them. In LADA (latent autoimmune diabetes of adults), something similar may happen at a much slower pace. In the group of diabetes types classed as MODY (maturity-onset diabetes of the young), one or another gene stops doing what it needs to do to produce insulin or make it work.

But in the average person with Type 2, it’s not so clear what happens. Why is the phase 1 response so weak in some people? Why do others have a reasonable bolus response but almost no basal insulin? Some think that the effect of insulin resistance wears the beta cells out, so they don’t produce enough. If muscles and the liver are resisting insulin, the basal level will need to be higher. Beta cells may work so hard to keep up high levels of basal insulin that they can’t produce more for bolus storage. Jenny Ruhl has a fuller explanation here.

But insulin resistance is itself a complicated thing, different in the muscles than it is in the liver and in fat cells. Many people have major insulin resistance and still never get diabetes. Many scientists think there is always some kind of insulin production problem, or sugars wouldn’t rise high enough to count as diabetes.

After decades of study, it’s fair to say nobody fully understands what causes insulin resistance, beta-cell damage, or insulin signaling problems. Someone who is not producing basal insulin will probably need some, unless metformin keeps their blood glucose levels low enough.

Problems with bolus insulin can often be effectively handled in Type 2 by high-fiber, low-starch-and-sugar diets and physical activity. Drugs like the incretins (Victoza [liraglutide], Byetta [exenatide], and Bydureon [exenatide XR]) may help with insulin signaling. Many foods (for example, vinegar) and herbs help some people.

And that’s as much as I know. If you know more, please share.

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