Diabetes, the gut and an unlikely protein

Ottawa scientists unveil new leads into diabetes research

By Amy Thatcher and Calvin Miller

Some of the greatest medical breakthroughs have been accidental — a combined result of serendipity and luck. Sir Alexander Fleming discovered Penicillin, a mold-based antibiotic, on some dirty petri dishes he forgot to clean.

Engineer Wilson Greatbatch discovered the pacemaker when some mixed-up pieces of electrical hardware began emitting a rhythmic pulse much like a heartbeat.

Could a similar event have happened this past year at the Ottawa Hospital Research Institute? Local scientists peering through a microscope in an Ottawa lab made a surprising—if not serendipitous—discovery.

They found an unlikely bacteria-killing protein residing in the pancreas: the key organ involved in diabetes.

“We think this protein is there naturally, but it’s playing a different role than being an anti-microbial,” says Fraser Scott, a senior diabetes researcher and professor at the University of Ottawa. “It actually stimulates the production of insulin.”

It was an entirely new finding,” says Scott. “Nobody had ever reported this before.”

 

A stimulating discovery
 

Scott has been studying the mechanisms of Type 1 diabetes (also known as juvenile diabetes) for 35 years. He and his team believe environmental factors such as diet, viruses, and gut bacteria play a vital role in determining who ends up with the disease.

As part of that research, a student working under Scott was examining a slide with two tissue samples under a microscope. The first sample—gut tissue—was expected to be teeming with an anti-microbial protein called cathelicidin antimicrobial peptide (CAMP). The second—a sliver of pancreas—was meant to act as a control.

Since the pancreas is an isolated organ nestled in the abdominal cavity behind the stomach, it’s never exposed to bacteria found in the outside world. Because of its sterile nature, it doesn’t need to have bacteria-killing proteins like CAMP to get rid of dangerous pathogens.

So when the student looked through the microscope and saw CAMP not only on the gut tissue, but also on the pancreas tissue, the researchers were left confused and slightly baffled.

It was an entirely new finding,” says Scott. “Nobody had ever reported this before.”

The team immediately began investigating the effect of CAMP on the pancreas, and quickly realized it helped Type 1 diabetic rats begin to produce insulin again. They also saw that CAMP began to regenerate some of the damaged insulin-producing beta cells.

“The big question is if we administer this to patients with diabetes, does it make it so they require less insulin…or even reverse the diabetes?” says Scott.

A gut reaction

Type 1 diabetes is an autoimmune disease, meaning the body attacks its own insulin-producing beta cells, rendering them useless. Because of this, most diabetes research has focused on lowering the body’s immune response to protect these cells.

But despite huge amounts of research, diabetes is still very much a mystery according to Patrick MacDonald, a researcher at the University of Alberta’s Diabetes Institute.

“There’s still a lot of work going into figuring out human diabetes,” he says. “This discovery adds an important piece to the puzzle about how islet cells grow and how diabetes may occur.”

Although CAMP showed promising regenerative effects for beta cells, it may not be a silver bullet solution for diabetes.

“It seems that CAMP may have the potential to create more healthy islets that are less likely to trigger an immune reaction,” says Colin Anderson, an immunology expert and professor at the University of Alberta. “But regenerating islets will only be useful if the autoimmune response that killed the them in the first place is stopped.”

Anderson also pointed out the value in pursuing research on the relationship between gut bacteria and various autoimmune diseases, emphasizing that “this link may be most relevant in Type 1 diabetes.”

Scott himself noted an interesting and important side effect of CAMP: when the protein was given to the diabetic rats, not only did their insulin production increase, but their micro-biomes seemed to shift to a more stable state. Thus far, Scott had no explanation for this curious side effect.

Both Scott and MacDonald emphasize the need for more research on how diabetes is affected by CAMP and the gut micro-biome.

“It’s easy to think of research in terms of finding what can be used as a drug,” says MacDonald. “But it’s equally important to understand how the disease works in the first place.”