First-Phase Insulin

First-phase insulin release is beginning to get the recognition it deserves. But we still have a long way to go to understand it.

“It’s a bit esoteric,” Dr. Alain Baron, Amylin Pharmaceuticals’ senior vice president of research, told me Friday. “Most physicians don’t understand its significance.”

Amylin’s new drug, Byetta, is the only drug that we have yet that stimulates first-phase insulin release. But at least two other groups are working on it.

When you eat a meal, one of the first things that you want to do is suppress the glucose production by the liver that is dumping glucose into the bloodstream, Dr. Baron explained to me. The reason why your blood glucose doesn’t go down to very low levels overnight is that the liver puts out glucose.

But when you eat breakfast, glucose is coming in to your bloodstream from your stomach. If at that point if the liver didn’t shut down, you would have two sources of glucose coming in, one from the liver and one from the food. And those two together would overwhelm the beta cells.

So the first thing that you want to do when you start eating is to suppress the hepatic glucose production by the liver. The first-phase insulin release is critical to that. And that first-phase insulin release floods the liver with insulin and very rapidly suppresses hepatic blood glucose production. This allows us to assimilate foodstuff into the bloodstream without causing our blood glucose levels to shoot up after meals.

This first-phase insulin release is one of the first things that people with diabetes lose. In healthy people our bodies release insulin within 10 minutes after eating. Sometimes people call it first-phase insulin response or secretion, but it’s different terms for the same thing.

Even if you don’t take Byetta, you may soon be able to get back your normal first-phase insulin release. Mannkind Corp., founded by insulin pump pioneer Al Mann, is developing inhaled insulin that approximates the natural first-phase insulin release.

This super-fast acting insulin works much quicker than any insulin we now have available. Full disclosure: I own stock in this company.

Another player in this field is one of my heros, A.H. (Tom) Clemens. Tom invented the very first blood glucose meter that we can use to test our levels. He invented the Ames Reflectance Meter in the late 1960s, and the first people with diabetes were able to use it in the early 1970s, as I wrote seven years ago in the Diabetes Wellness Letter.

Tom is still actively researching diabetes and ironically didn’t have diabetes himself until recently. “I have made first-phase insulin secretion the goal of my life for the past 30 years,” he told me on the phone today.

His oral presentation at the American Diabetes Association’s scientific sessions just concluded in Chicago reported on the success of that work in an oral presentation. The abstract, 281-OR, is online at “Restoration of Native Incretin Activity.”

Studying rhesus monkeys, Tom succeeded in restoring native incretin activity. He uses a small molecule that doesn’t need to be injected. Just one dose per week can restore our first-phase insulin secretion by correcting a metabolic imbalance. The new diabetes drug, which he calls GNTI (short for 5′-guanidinonaltrindole), is an indole derivative of naltrindole and is a synthetic opioidergic compound.

This is esoteric. But this important research is making it a lot easier to control our diabetes.

This article is based on an earlier version of my article published by HealthCentral.