Bright, shiny objects

Medicine has ignored the vital role that glucagon plays in diabetes

Are you ready to play What Am I? According to Google Play, it’s “a word guessing and multi-activity game that can entertain you and your friends for hours without [you] noticing the time.”

Missed your wedding? Of course you did; you were playing What Am I? Didn’t make the plane for your family holiday? Just tick the “What Am I?” option on your travel insurance claim form for a full refund.

So, let’s play the game with a medical twist. “I am a hormone produced by the pancreas to regulate glucose (blood sugar) levels. What am I?”

If you answered “insulin,” join the vast majority who have also gotten it wrong. Don’t fret. All of medicine, including doctors and endocrinologists, also got that one wrong. But as diabetes is the precursor of heart disease, which is still the world’s major killer, it could be worth getting this one right. Just saying.

The correct answer is glucagon. Insulin reduces levels of glucose from carbohydrates, but it’s glucagon that raises and regulates glucose levels. Understanding that two hormones, and not one, play a vital role in glucose regulation and the onset of diabetes changes the way we treat conditions such as hyperglycemia (high blood sugar)—or it should.

So, how have we ignored a vital hormone? Welcome to medicine’s world of bright, shiny objects. “Insulin dogma,” as some call it, was born in 1922 when Canadian biochemist Frederick Banting produced one of the shiniest ever by injecting a wasted young boy with his discovery: insulin. Within months, the boy had turned into a strapping lad, as every newspaper around the globe reported.

They showed before-and-after pictures of him with headlines like “The Best Christmas Present of Them All.”

And Banting was awarded another bright, shiny object a year later: the Nobel Prize in Physiology or Medicine.

Glucagon is the “Cinderella hormone” that was discovered the same year Banting traveled to Stockholm to pick up his award. As they worked to isolate insulin, researchers were noting an “impurity” in laboratory tests that raised blood glucose levels. They called it glucagon and dismissed it as a contaminant of little value to our metabolism.

A small handful of researchers thought it was more significant. Leading the field was Rolf Luft, a titan of medical research in endocrinology and diabetes, who consistently pointed out the importance of glucagon but was roundly ignored.

His mantle was taken up by Roger Unger, director of the Touchstone Center for Diabetes Research at UT Southwestern. As an advocate of the “bihormonal hypothesis,” as it became known, Unger postulated that glucagon excess, rather than insulin deficiency, is essential for the development of diabetes. But, as we know, mainstream diabetes care focuses on insulin regulation—that’s only half the story, though.

Like insulin, glucagon is produced by the pancreas and released into the bloodstream when blood sugar levels drop. It works by stimulating the liver to convert stored glucose into a usable form and by preventing the liver from storing glucose.

Glucagon also helps the body make glucose from other sources, such as amino acids. As researchers later discovered, hyperglycemia is as much related to low insulin, which lowers blood glucose, as it is to high glucagon, which boosts glucose production.

Why has medicine been so dazzled by the bright, shiny object of insulin? Unger reckons it’s to do with a phenomenon he called “dogma displacement inertia.” Although there’s been mounting evidence of glucagon’s vital role in glucose control since he was able to isolate it in 1950, medicine went so far down the insulin rabbit hole that it’s only just beginning to see a way back.

One drug company has finally been paying attention to Unger. Novo Nordisk has pioneered a family of drugs called GLP-1s (glucagon-like peptides). They work by mimicking the actions of GLP-1, a hormone that helps the body release insulin and suppress glucagon. As the basis of the weight loss drug Wegovy, this product has turned the company into the biggest in Europe.

To round things off, a final What Am I? question: “I am a series of dogmas that parade as a science, driven by the drug industry and its profit motive. What am I?” Well done. You all got that one right— it’s medicine.

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