The End of Insulin: Research Is Bringing Us Closer to a Cure Than Ever Before

Illustrations by Jordan Carson

November is National Diabetes Awareness Month! As part of the celebrations, we're revisiting five great stories showcasing the breadth of work being done at the University of Alberta in the journey towards a cure. The following story was originally published on June 18, 2021

For many of the 465 million people around the world living with diabetes, insulin is a lifeline.

Since their bodies don’t produce enough of the hormone naturally — or can’t properly use what they do produce — a strict regimen of daily injections helps people with Type 1 diabetes and around a tenth of people with Type 2 diabetes ward off life-threatening health problems.

The University of Alberta has had a hand in insulin research since the beginning, when biochemist James Collip, ’24 PhD, ’26 MD, ’46 LLD (Honorary), first purified a type that could be injected into patients with diabetes to combat excess sugar in the blood. That was a century ago. Since then, U of A researchers have vaulted off Collip’s life-changing discovery to develop better treatments for diabetes, including the Edmonton Protocol.

While insulin has saved countless lives, it’s not a treatment to take lightly. Many people with diabetes live under the fear of a slip-up — an over- or under-dose that could end in a seizure, coma or death. Insulin is a lifeline, but it’s not a cure.

Five researchers at the Alberta Diabetes Institute (ADI) are bringing us closer to a cure than we’ve ever been. From harnessing stem cell technology that sends blood back in time to mobilizing microparticles that bring islet cells back from the dead, these research projects aim to reverse diabetes and eliminate the need for insulin.

This research is made possible through critical funding partners including Diabetes Research Institute Foundation of Canada, the Alberta Diabetes Foundation, the Stem Cell Network of Canada, the Weston Family Foundation, as well as hundreds of community supporters.

Rewind the clock, and retrain your body to work for you

James Shapiro and his U of A team created a global standard for diabetes treatment with the Edmonton Protocol. Two decades later, he’s using stem cell therapy to tie up the loose ends on a cure.

How it works

Stem cells have the ability to transform into any type of cell if nudged in the right direction. Shapiro and his team will genetically engineer a patient’s own blood cells to revert into stem cells and then reprogram them to become insulin-producing islet cells. These islets will be transplanted into the patient’s liver, where they will produce insulin. The “super-liver” will replace the normal functions of the pancreas. Since the cells are the patient’s own, there’s no need for the anti-rejection drugs that accompany traditional transplants.

Yesterday’s research, tomorrow’s treatment

Shapiro’s research is the capstone on a treatment he and a team of researchers with the Clinical Islet Transplant program developed 22 years ago at the U of A — the Edmonton Protocol, which gives patients islet transplants from organ donors. While it remains a global standard for diabetes treatment today, it has its hangups. Patients need to take immunosuppressants for life, which can cause a host of serious and long-term side effects. And with the number of people living with diabetes expected to skyrocket to 700 million by 2045, there will never be enough donor islets to go around. Today, only people living with the severest forms of diabetes are eligible for a transplant.

What a cure looks like

Shapiro, professor of surgery and Canada Research Chair in Transplantation Surgery and Regenerative Medicine, has high hopes. He dreams of seeing all people living with diabetes cured within seven years — starting with the most vulnerable populations in Canada who don’t have access to proper care. A cure would save Canadians with diabetes an average of $1,500 per year on out-of-pocket expenses on prescription drugs and devices. For the Canadian health-care system, the annual savings would ring in at $3.8 billion.

A two-for-one solution with a hefty reach

Andrew Pepper and Gregory Korbutt are working to make islet transplants safer and more accessible, closing in on a cure for the masses.

How it works

Islet transplants pave a promising path toward the end of insulin. But viable donor islets are hard to come by. Korbutt and Pepper have identified a reliable supply of islet cells from neonatal pigs that can be transplanted into patients with diabetes. Patients would receive localized anti-rejection drugs directly to the cells instead of throughout the whole body, which would thwart the usual side-effects (like ulcers, weakness and infection) caused by immunosuppression.

Yesterday’s research, tomorrow’s treatment

Two giants stand between islet transplants and a cure: limited islet supply and the severe side effects of anti-rejection drugs. Korbutt and Pepper are socking them both with one swing. Since immunosuppressants can pose more risk than reward, currently “only about five to 10 per cent of patients living with diabetes are eligible for a transplant,” says Pepper, an assistant professor in the Department of Surgery. He and Korbutt have developed a way to carry anti-rejection drugs directly to the site of the transplant using microscopic bubbles that will release over time to keep the immune response at bay. The islets themselves will come from pigs, which have already been successfully used for heart and kidney cell transplants. Korbutt, one of the original members of the Edmonton Protocol team and now the scientific director of the U of A's Alberta Cell Therapy Manufacturing, has been researching the viability of neonatal pig islets for 20 years. If this new, massive supply of donor cells is unlocked for human use, it would throw the doors of eligibility for this treatment wide open.

What a cure looks like

Diabetes is on the rise — particularly in lower- and middle-income countries — and it’s the direct cause of more than 1.5 million deaths per year worldwide. With Korbutt and Pepper’s innovations, patients receiving an islet transplant will no longer have to combat the side effects of immunosuppressants. And they won’t have to worry about their body rejecting the transplant. Most importantly, with a much larger supply of insulin-producing islet cells available, access to a cure could reach all corners of the Earth.

This pill has the power of resurrection

Jean Buteau is developing a drug that can stop insulin-producing cells from decaying, and bring dead cells back to life.

How it works

Buteau and his team have identified a gene in insulin-producing cells that determines whether the cell lives or dies. They’ve also found a drug that can trigger this gene on command. This pill would protect existing insulin-producing cells from dying and regenerate cells that had been previously destroyed by the immune system.

Yesterday’s research, tomorrow’s treatment

The drug has already proven to be successful on patients with Type 2 diabetes. As a result, Buteau can fast-track clinical trials on patients with Type 1 diabetes, ramping up the pace in the race for a cure. The pill is the only medication on the market that can control the life or death of an insulin-producing cell, and the clinical expertise and facilities at the Alberta Diabetes Institute can help Buteau get this pill into the hands of people living with diabetes. “It continues a tradition of excellence that we have [at the U of A], including the discovery of insulin and the Edmonton Protocol,” he says. “It’s critical that we continue that line of impactful discoveries for diabetes.”

What a cure looks like

People with diabetes face serious health challenges outside of managing their insulin. They’re three times more likely to be hospitalized with cardiovascular disease and 20 times more likely to be hospitalized for lower limb amputation. Diabetes is also among the leading causes of kidney failure. Buteau’s treatment has the potential to regenerate a person’s ability to produce their own insulin, liberating them from the health complications associated with the disease and creating a future without diabetes.

Stop diabetes before it starts

Andrea Haqq is harnessing the power of a proven therapy and a multidisciplinary team to prevent Type 2 diabetes in youth.

How it works

Childhood obesity is a precursor to insulin resistance and eventually Type 2 diabetes. Haqq’s treatment uses a combination of dietary fibre and metformin — a drug already used to treat Type 2 diabetes in adults — to reverse obesity and insulin resistance and prevent Type 2 diabetes in children.

Yesterday’s research, tomorrow’s treatment

Metformin has been used to treat Type 2 diabetes in adults since 1957, however it hasn’t been successful in children. Haqq, a clinician-scientist at the Alberta Diabetes Institute and professor of pediatrics at the U of A, took a different approach to the drug. She and her team are using metformin alongside dietary fibre to reprogram the gut microbiome in children in a way that curbs insulin resistance. Haqq was able to pursue this line of research because of the collaborative team and clinical testing facilities at the Alberta Diabetes Institute. Their work has set the stage for a preventative therapy with the potential to reverse insulin dependence and prevent diabetes in children.

What a cure looks like

People with Type 2 diabetes make up 90 per cent of all people living with the disease. And unlike Type 1 diabetes, Type 2 can be prevented. In the past 30 years, Type 2 diabetes among children has doubled, according to medical journal The Lancet. Without a cure, prevention is the only line of defence between children and the lifelong dangers of diabetes. Haqq’s preventative treatment goes beyond diet and exercise to sever the chain that anchors children to Type 2 diabetes, helping them live long and healthy lives, no lifeline required.