Insulin

The Royal Canadian Mint has released a new two-dollar coin commemorating the discovery of insulin 100 years ago by scientists at the ��Ƶ.

The coin features a monomer, a building block of the insulin molecule, as well as red blood cells, glucose, insulin cells and the scientific instruments – vial, mortar and pestle, Erlenmeyer flask – used in the early formulation of insulin.

“The Nobel Prize-winning Canadian discovery of insulin in 1921 is one of the 20^th century’s most celebrated medical discoveries, which has saved millions of lives in Canada and around the world,” Chrystia Freeland, Canada’s deputy prime minister and minister of finance, said in a statement.

Scientists Frederick Banting, Charles Best, J.J.R. Macleod and James Collip worked together to isolate and purify insulin in a U of T laboratory. Isolation of the hormone transformed medical outcomes and dramatically improved the quality of life for diabetes patients, who were previously debilitated by the disease.

U of T is celebrating the 100th anniversary of the discovery this year with a slate of events. The university hosted an Insulin100 Scientific Symposium that brought together the world’s leading diabetes researchers and the Thomas Fisher Rare Book Library mounted an online exhibition that highlights its collection of original documents relating to the history of insulin research.

U of T staff and faculty also contributed to the creation of a commemorative stamp and a Heritage Minute paying tribute to the anniversary.

The Royal Canadian Mint has issued two million coins with the insulin design in colour and another million without colour. The coins were designed by Jesse Koreck, an artist from Waterloo, Ont.

“This commemorative circulation coin is a heartfelt and enduring ‘thank you’ to the talented researchers behind a Canadian breakthrough that has saved millions of lives over the last 100 years, and continues to do so today,” Royal Canadian Mint President and CEO Marie Lemay said in a statement.

Towards a cure: Insulin100 scientific conference draws world’s leading diabetes researchers

Christopher.Sorensen — Wed, 21 Apr 2021 20:21:35 +0000

Towards a cure: Insulin100 scientific conference draws world’s leading diabetes researchers

Christopher.Sorensen Wed, 04/21/2021 - 16:21

Cutline

The Insulin100 Scientific Symposium drew diabetes experts from around the world to discuss research, patient perspectives and access to treatments (photo by Marian Vejcik via Getty Images)

Yanan Wang

Topic

Global Lens

Leslie Dan Faculty of Pharmacy

Patient stories. Innovative diabetes therapies. A peek inside the bedroom of one of the scientists who discovered insulin at the ��Ƶ.

Those were just a few highlights of U of T’s recent Insulin100 Scientific Symposium, which drew more than 6,000 attendees from around the world.

The two-day scientific symposium commemorated the 100th anniversary of the discovery of insulin in a U of T laboratory – and was preceded by a public celebration one day earlier that featured stirring videos from diabetes patients across the globe who spoke about the role of insulin in their lives.

“I’m thankful for insulin because it allows me to keep playing tennis,” said one U.S. woman. “I am thankful for insulin because even though I’m diabetic, it still means I can eat great food,” said a man from the U.K. “I’m thankful for insulin because I can travel,” a woman from New Zealand said.

In 1921, Ontario surgeon Frederick Banting, then-U of T student Charles Best and U of T alumnus James Collip, working under the direction of U of T physiology professor J.J.R. Macleod, extracted the peptide hormone that revolutionized diabetes treatment, making the metabolic disease manageable through insulin.

Attendees at the public celebration also received an account – delivered by the curator of the Banting House in London, Ont. – of the moment Banting arrived at his world-changing idea in the middle of the night, complete with a photo of his wallpapered bedroom.

Yet, as Banting himself said during the lecture for his 1923 Nobel Prize in Physiology or Medicine, insulin is not a cure.

As a result, a major thrust of the scientific symposium focused on the innovative scientific research that will hopefully one day relegate a disease that affects 420 million globally to the dustbin of history.

Daniel Drucker and Gillian Hawker, both professors in the department of medicine in U of T’s Temerty Faculty of Medicine, kicked off the scientific symposium by moderating a panel with scientists from three major pharmaceutical companies engaged in diabetes research.

“What we are really looking forward to is to apply the powerful science that has become evident in the last few years to move beyond insulin toward a cure,” said Drucker, who is also a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health and a recent recipient of the Canada Gairdner International Award.

“How are your companies going to potentially cure diabetes?”

The scientists – from Eli Lilly and Company, Novo Nordisk and Sanofi – proposed stem cell-based approaches and immunotherapies that are in their early stages of development. They also raised the possibility of screening and preventing type 1 diabetes before it manifests as a way to substantially reduce the incidences of disease.

In the nearer term, conference attendees also spoke about the need to improve access to affordable insulin and other treatments for diabetes patients around the world, including in wealthy countries like the U.S.

“That’s unforgiveable, to have people take a suboptimal dose of insulin because they can’t afford the therapeutic dose,” Bernard Zinman, a professor in U of T’s department of medicine and a senior scientist at the Lunenfeld-Tanenbaum Research Institute, told symposium attendees.

Experts also noted that, because insulin is temperature-sensitive and has a short shelf life, maintaining supply in remote regions is particularly difficult. It can also be challenging to make new devices and other therapies available to resource-limited parts of the world, they said.

“The burdens and opportunities are different from country to country for people with diabetes,” said Dana Lewis, an insulin-dependent diabetic and University of Alabama alumna who created an open-source artificial pancreas system that automates micro-adjustments of insulin delivery to the body.

The issue of equitable access was addressed in a presentation by Jean Claude Mbanya, a professor of medicine and endocrinology at the University of Yaoundé I in Cameroon. Mbanya outlined how the absence of government policies, mark-ups in the supply chain and the organization of diabetes management within health-care systems can all impact patient access to insulin.

John Buse, the Verne S. Caviness Distinguished Professor at the University of North Carolina School of Medicine, gave a presentation on the future of insulin management in type 2 diabetes. He pointed out that while insulin has higher efficacy than many of the alternative drugs now available for type 2 diabetes, it has also been associated with weight gain and hypoglycemia (low blood sugar).

“The landscape has changed, and insulin has gone from being the only therapy available for type 2 diabetes beyond lifestyle management, to one that has advantages and disadvantages,” said Buse, who directs the diabetes centre at his university and who won the 2019 American Diabetes Association Outstanding Achievement in Clinical Diabetes Research Award.

Other approaches, including GLP-1 therapies, have comparable efficacy to basal insulin without the same adverse effect of hypoglycemia, Buse said, declaring it a “tie” between the two treatments.

“Insulin therapy is often necessary, but rarely preferred in the setting of type 2 diabetes due to weight gain, hypoglycemia, general complexity of initiating and titrating therapy, and lack of clear-cut cardiovascular benefits,” he said.

The U of T laboratory where insulin was discovered (photo courtesy of the ��Ƶ Archives)

James Shapiro, a professor at University of Alberta who was the first in Canada to start clinical trials with human embryonic-derived insulin-producing stem cell transplants, spoke on the future of pancreas and islet transplantation.

“Islet transplant has the capacity to cure diabetes,” Shapiro said.

Shapiro added, however, that the approach is currently limited by the number of cells that can be acquired from an organ donor and risks linked to the anti-rejection drugs required for a transplant –challenges he’s working on solving with other scientists and biotechnology companies.

“This is my firm belief: diabetes will become a thing of the past if all goes according to plan,” he said.

In addition to the work of leading scientists in the field, the scientific symposium also recognized the work of trainees and early-career researchers who are making significant contributions to diabetes scholarship.

Awards were given to graduate students, post-doctoral researchers and early-career researchers studying diabetes. They included: Imperial College of London’s Steven Millership, Rebecca Cheung and Grazia Pizza; McMaster University’s Marie Pigeyre; Aviroop Biswas, an assistant professor at U of T’s Dalla Lana School of Public Health; and Saad Khan, a U of T doctoral student in immunology who studies links among the immune system, inflammation and obesity in metabolic diseases.

Drucker ended the symposium on a hopeful note by calling for a day when insulin therapy is no longer needed.

“The science that I heard in the last two days gives me tremendous optimism,” he said. “Let’s try to eliminate type 1 diabetes, so there is no 125th anniversary.”

Insulin 100: U of T researchers work on novel drug therapies for diabetes, other illnesses

Christopher.Sorensen — Fri, 16 Apr 2021 21:09:09 +0000

Insulin 100: U of T researchers work on novel drug therapies for diabetes, other illnesses

Christopher.Sorensen Fri, 04/16/2021 - 17:09

Cutline

From left to right: Leslie Dan Faculty of Pharmacy researchers Stéphane Angers, Shana Kelley, Shirley Wu, Carolyn Cummins and Marisa Battistella.

Topic

In the 100 years since Frederick Banting and Charles Best discovered insulin as a treatment for diabetes, the process of drug discovery has changed radically – from lab equipment to techniques and technology.

But pharmaceutical scientists’ drive to develop life-saving drugs remains as strong as ever.

“Insulin is a phenomenal example of how important drug discoveries can change the lives of people all over the world,” says Lisa Dolovich, dean of the ��Ƶ’s Leslie Dan Faculty of Pharmacy.

“We’re really proud to be working on therapeutic discovery and new diagnostics that we hope will also have significant impacts on people’s health and quality of life.”

Whether focused on diabetes or other conditions, researchers at Leslie Dan are part of a culture of innovation and discovery inspired by Banting and Best that benefits from the faculty’s breadth of expertise and research approaches.

“It provides new opportunities and new ways of thinking to infuse our different labs because people can learn from one another,” says Dolovich. “And, of course, we benefit from having students who have been educated in different areas, all coming together in pharmaceutical sciences.”

Here are five researchers at the Leslie Dan Faculty of Pharmacy who are pushing the boundaries when it comes to drug treatments for diabetes and other diseases:

Understanding mechanism of drug-induced diabetes may lead to new treatments

One of the first stages of drug discovery is understanding cellular pathways and what goes wrong in different conditions in order to find ways to counteract these effects.

“Part of my research is trying to discover new drug targets and then collaborating with chemists to make small molecules that we hope might eventually be turned into therapeutics,” says Carolyn Cummins, an associate professor at the Leslie Dan Faculty of Pharmacy. “This drug discovery research is central to the pharmaceutical sciences.”

Cummins studies how glucocorticoids – stress hormones that are often prescribed as anti-inflammatory drugs – cause drug-induced diabetes. These drugs activate a receptor in the liver that stimulates the body to produce glucose, and, if they are taken chronically, predispose patients to conditions such as obesity and diabetes.

Her work focuses on the nuclear receptors involved in the glucocorticoid signalling pathways. A better understanding of how these signalling pathways work and what happens when they are overstimulated may suggest new drug targets and a way to dose the anti-inflammatories to avoid this side effect.

Although her work is at the early stages of drug discovery, she says her research is still informed and broadened by considering the patient perspective.

“As pharmaceutical scientists, we have the capacity to learn about the patient perspective because we have access to front-line clinicians and pharmacists,” she says.

Clinical collaborations key to moving research forward

Interacting and collaborating with clinicians is a key element of Shana Kelley’s research, enhancing her ability to make new breakthroughs and allowing her to see first-hand the challenges related to curing disease.

“If you go to see a collaborator at a hospital, you cannot miss seeing the people who are there to receive care,” says Kelley, a University Professor. “We have a very collaborative clinical community in Toronto, and it is such a huge resource for people like me, but it also keeps the patients top of mind.”

Kelley and her team develop technologies that use molecular biology and nanotechnology to detect and diagnose disease – and look for drug targets in large volumes of sample – and they frequently collaborate with clinicians to access patient samples. Much of their work has focused on systems that scan large populations of cells to look for specific genetic sequences or mutations, which can be used for early detection of diseases such as cancer.

Kelley’s team isn’t focused on a single disease. They apply their expertise to solve problems that apply to different types of conditions.

“Pharmaceutical science is a broad field, and it’s very inclusive,” says Kelley. “In our faculty, we feel really strongly about solving critically important problems, and so it has a culture that lends itself to discovering new things and developing new technologies.”

The focus on applying discoveries to solve problems is a particular strength of the Leslie Dan Faculty of Pharmacy, according to Dolovich.

“We see beyond the boundaries of one medical area or one condition and look at these problems from the drug perspective or from the device perspective,” she says. “We can build on discoveries that have happened within the context of one medical condition [so it can be] considered for others.”

Drug delivery technologies for improving patient health

Professor Shirley Wu and her team develop new drug delivery technologies to ensure drugs reach their intended targets in the body.

The research is multidisciplinary and can be applied to many different diseases, so collaborations with experts in these diseases is essential.

“A lot of work can’t be done with just one lab,” says Wu. “We have the technology to improve drug delivery, but we need other people’s expertise to understand the biology and assess what we develop.”

Wu’s team has led work relating to a number of conditions, including cancer, diabetes and Alzheimer’s disease.

To improve insulin therapy in diabetes, her team has studied intelligent insulin delivery over the last two decades. Recently, they developed a “smart” microneedle patch to help people with diabetes manage hypoglycemia, a potentially dangerous complication of insulin therapy. The patch senses low blood sugar levels and, in response, automatically releases the hormone glucagon, which raises blood sugar levels. The non-invasive and painless device is currently in preclinical development.

Wu says that her team approaches research with the intent to make a difference for patients.

“We want to improve patient care, their health and their lives,” says Wu. “After we published the first paper on the microneedle patch, we received multiple emails from patients and relatives asking when and where we were going to run clinical trials. This is an in-demand treatment, which motivates us to work harder and faster toward clinical use.”

Advanced biologics may help treat complications of diabetes

When insulin was discovered 100 years ago, it was the world’s first biologic treatment that used a protein to treat disease. A century later, researchers at U of T are also developing advanced biologics to help treat conditions such as diabetic retinopathy, an eye condition that can cause vision loss and blindness that affects about a third of people with diabetes.

An impermeable physiological barrier in blood vessels around the eye – the blood-retina barrier – protects the eye from molecules circulating the body through the blood. But in diabetes, high blood sugar levels cause the barrier to “leak,” damaging the retina and causing blindness.

“Right now, there are limited drugs to treat diabetic retinopathy and they don’t work for everyone, so there’s an urgent need to develop other medications that could benefit patients,” says Stéphane Angers, professor and associate dean of research. “We’re developing a biologic that uses a completely different mechanism than the existing treatment, and our preclinical research shows that this biologic is very powerful for promoting barrier function.”

Angers and his team developed an antibody that regulates a signalling pathway involved in blood-retina barrier function in order to strengthen the barrier. To help bring this biologic treatment to the clinic, he has launched a start-up company to complete the preclinical work, and he hopes that the drug will be ready to start clinical trials within a couple of years.

“Our Toronto-led effort to develop a biologic for people with diabetic retinopathy follows the legacy of Banting and Best,” says Angers. “Being in a drug discovery ecosystem, we’re ideally positioned at the [Leslie Dan Faculty of Pharmacy] to develop new drugs and translate our research into drug therapies.”

Clinical experience informs drug discovery process

Just as researchers aim to move discoveries into the clinic, clinician-scientists also bring their front-line perspectives back to drug discovery.

“Because we have health professionals and students learning and working alongside those who are focused on scientific discovery, we can cross the bridge from drug discovery to health care,” says Dolovich. “It allows us to think about how new drug discoveries are going to impact patients and their care and the professionals who deliver that care. All that information feeds back into the drug discovery process.”

Marisa Battistella is a pharmacist and clinician-scientist specializing in chronic kidney disease (CKD). “People with diabetes are at higher risk for other conditions, including CKD, and often take many different types of medication, which may result in drug interactions,” she says.

Battistella’s research focuses on pharmacy practice, including using genomics to guide drug selection and optimizing patient medications, which may also include de-prescribing.

She says having clinical and basic scientists working together helps to spur innovation in drug discovery.

“Clinician-scientists and basic scientists are all trying to improve patient care – that’s our ultimate goal. Having these collaborations is really important and they can inform each other in ways to improve research and patient care,” she says. “I have the relationships at the hospital to roll out discoveries made in the lab, but we can also explain to researchers at the faculty how we translate research or clinical studies into practice.”

Battistella is also active in education, not only as a course instructor and co-ordinator, but also serving as a preceptor and mentor. “Students often ask really good questions or they dig deeper into a particular disease or medication,” she says. “Their questioning minds help inform my thinking and help me to think deeply and consider ideas or research questions we could pursue.”

With nearly four million Canadians living with diabetes and this number projected to grow over the coming years, U of T students studying both pharmacy and pharmaceutical sciences will play active roles in improving diabetes care in the future, says Dolovich.

“We’re proud that we graduate pharmaceutical scientists and pharmacists who will be in a position to help people with diabetes, whether it’s in community pharmacy, in hospital, or research settings,” she says. “We do our best to prepare our students to take up the challenge and contribute as integral members of the health-care team.”

Commemorative stamp marks 100th anniversary of U of T’s discovery of insulin

Christopher.Sorensen — Thu, 15 Apr 2021 14:25:09 +0000

Commemorative stamp marks 100th anniversary of U of T’s discovery of insulin

Christopher.Sorensen Thu, 04/15/2021 - 10:25

Cutline

Canada Post unveiled the new stamp at an online symposium sponsored by Diabetes Action Canada, U of T’s Banting & Best Diabetes Centre and the department of medicine in the Temerty Faculty of Medicine

Geoffrey Vendeville

Topic

Among the treasures in the ��Ƶ’s archives are letters from grateful diabetic patients and their families addressed to Frederick Banting, who, along with Charles Best, J. J. R. Macleod and James Collip, discovered the role of insulin in the disease.

So, it’s fitting that this year’s celebrations marking the 100th anniversary of the medical breakthrough at U of T include a new Canada Post stamp.

The stamp, unveiled this week at a virtual celebration held by Diabetes Action Canada, U of T’s Banting & Best Diabetes Centre and the department of medicine, features an excerpt from Banting's unpublished memoir and an original insulin bottle with a red cap.

U of T researchers Scott Heximer and Patricia Brubaker worked with Canada Post and Banting House to ensure the stamp’s historical accuracy and help source archival material.

“When we got into this, we didn’t realize everything that went into making a stamp,” says Heximer, an associate professor and chair of the department of physiology in the Temerty Faculty of Medicine.

In addition to the stamp itself, the unveiling includes an official first day cover that also required fact-checking.

“It was fun,” says Heximer. “Our local committee was sitting around looking at pictures of Banting and letters addressed to the doctors in Toronto, and these were all things that went into building this official first day cover.”

One hundred years ago, Banting – a surgeon with a struggling practice in London, Ont. and little research experience – approached Macleod in U of T’s department of physiology in search of the support and equipment necessary to carry out his experiments. Macleod offered Best, who had recently graduated with a degree in physiology and biochemistry, the opportunity to work with Banting. Together with Collip, a biochemist on sabbatical from the University of Alberta, the researchers succeeded in producing a pancreatic extract from cattle that prevented death from diabetes.

Brubaker, a professor in the departments of physiology and medicine, notes that the influence of Banting, Best, Collip and Macleod can still be felt in the department of physiology. For example, she says, Best was chair of the department when Professor Emeritus Mladen Vranic was hired.

Vranic, in turn, hired Brubaker, who won a lifetime achievement award from Diabetes Canada last year and whose research has contributed to the development of drug treatments for patients with type-2 diabetes. The drugs work by stimulating the secretion of insulin, helping to lower blood sugar levels and reduce appetite, among other effects.

In 1923, Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine. Banting was the first Canadian to win a Nobel and remains the youngest winner of the prize in physiology or medicine (he was 32). Banting and Macleod shared the prize with Best and Collip.

The discovery of insulin was such a monumental achievement that a stadium full of people listened to Banting discuss the research, according to Brubaker.

“It was considered not a cure for diabetes, but a cure for death due to diabetes,” says Brubaker, who lives with type 1 diabetes herself and has devoted much of her career to understanding the disease. “Type 1 diabetes was a death sentence – a slow, prolonged, painful death – and it affected mostly children.”

The announcement of a lifesaving treatment was especially welcome news after the end of the First World War and a global pandemic that, like today’s, killed millions.

“This was an exciting ray of sunshine,” Brubaker says.

In March 1922, a Toronto Star bold-face headline proclaimed: “Toronto Doctors on Track of Diabetes Cure.”

Soon, fan mail poured in for Banting and his colleagues.

Teddy Ryder, a five-year-old diabetic admitted to hospital weighing just 26 pounds, received his first insulin shots in January 1922. The next year, he wrote a letter to Banting in sprawling capital letters that filled the page. It said: “I wish you could come to see me. I am a fat boy now and I feel fine. I can climb a tree.”

Canada has issued stamps since 1851, though most early examples featured English royalty, according to Jim Phillips, director of stamp services at Canada Post. Since then, Leonard Cohen, Alexander Graham Bell and Viola Desmond are among those whose images have graced the tiny squares.

As for Banting, he was last featured on a Canada Post stamp in 2000.

“We see ourselves among the oldest Canadian storytellers,” Phillips said, adding that the discovery of insulin is a “fantastic story” for a stamp.

“These are real heroes, these four guys, and the ��Ƶ for backing them and giving them space for their research ... This is a very, very positive story – and I think we need positive stories more than ever right now.”

Insulin 100: How the road to a diabetes cure is yielding better treatments

Christopher.Sorensen — Thu, 01 Apr 2021 15:09:30 +0000

Insulin 100: How the road to a diabetes cure is yielding better treatments

Christopher.Sorensen Thu, 04/01/2021 - 11:09

Cutline

(Photo by Getty Images/iStockphoto)

Jim Oldfield

Topic

Institute of Biomedical Engineering

Faculty of Applied Science & Engineering

Banting & Best

Diabetes

Nutritional Sciences

Physiology

University Health Network

“The pancreas,” says Gary Lewis, an endocrinologist at Toronto General Hospital and director of the Banting & Best Diabetes Centre at the ��Ƶ’s Temerty Faculty of Medicine, “is like an exquisitely sensitive and perfectly networked computer.”

Second by second, he notes, the pancreas secretes just the right amount of insulin or glucagon to lower or raise blood sugar into the portal vein that leads directly to the liver, the site of key metabolic processes. Insulin is then distributed to every tissue in the body via general circulation.

“Insulin injections are life-saving, but administered under the skin and nowhere near as precise,” says Lewis, who is also a scientist and professor in the department of physiology and department of medicine at U of T. “It’s extraordinarily difficult to mimic the function of a healthy pancreas.”

That’s one reason a cure for diabetes has proven elusive 100 years after the discovery of insulin.

Another big reason is the complexity of how the disease arises. In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas, creating a life-threatening spike in blood sugar. Type 2 diabetes usually comes on more slowly, as the body becomes resistant to insulin or the pancreas can’t produce enough of it.

Genetics play a role in both types. Exposure to viruses and other environmental effects may be a factor in type 1. Lifestyle factors, including weight gain and physical inactivity, are strongly linked to type 2.

The bottom line, says Lewis, is that diabetes is a multifactoral disease, and we’re not close to a cure.

Ask about treatments, though, and Lewis gets excited.

The last two decades have brought a plethora of clinical and research advances, from new drugs to boost and sensitize the body to insulin and promote weight loss, to lifestyle interventions that improve diet, continuous monitoring of blood sugar, long- and short-lasting insulin, better insulin pumps, pancreatic transplants and pre-clinical stem cell and immunosuppressive therapies.

“Progress on treatments has been fantastic, especially for type 2,” Lewis says. “I’m very, very hopeful.”

The distinction between treatment and cure in medicine is often unclear. And for the 3.6 million Canadians living with diabetes, the distinction matters less and less if the goal is a full and healthy life.

Type 2 diabetes accounts for about 90 per cent of diabetes cases in Canada. Prevalence is rising, but Canadians with type 2 diabetes are living longer and have fewer diabetes-related complications.

“The clinic doesn’t look like it did 30 years ago,” says Lewis, who mainly treats patients with type 2. “We see fewer amputees, less blindness. Patients are generally healthier, and their prognosis is often excellent if they maintain their blood sugar target and other key parameters.”

Weight loss is a cornerstone of treatments to lower blood sugar, and recent research has strengthened the link between weight reduction and type 2 diabetes management. Some people with type 2 can lose weight and control blood sugar through dietary changes and exercise alone.

Bariatric surgery is very effective for weight loss and often results in diabetes remission, although it comes with surgical risks and is expensive.

“If we could prevent obesity, we could greatly reduce the incidence of type 2,” Lewis says. “And experiments have shown we can get a remission with lifestyle changes, so we know what works.”

The problem is broad implementation.

“I’ve tried to lose weight and I know how difficult it can be, especially in an environment of convenient and inexpensive calories,” Lewis says. Moreover, factors such as income, education, ethnicity, access to healthy food and living conditions can make lifestyle changes that curb obesity nearly impossible.

“Social determinants of health are overwhelmingly the most important influence on who gets type 2 diabetes, and how well or poorly they do with it,” Lewis says.

Fortunately, dozens of new drugs for diabetes have hit the market in the last two decades.

Medications for weight loss round out the armamentarium, and some also protect against kidney damage and lower cardiac risk. Current therapies can reduce body weight up to 10 per cent, although a loss of 20 per cent or more would have a greater effect on outcomes for patients with type 2 diabetes, says Jacqueline Beaudry, an assistant professor of nutritional sciences at U of T who studies links between obesity, hormones and diet.

Beaudry is probing the biology that underpins these medications, including the gut hormones GLP-1 and GIP. They control blood glucose and reduce appetite, but scientists are unsure how.

“If we could understand their mechanisms of action, we could design better drugs,” Beaudry says.

For people with type 1 diabetes, continuous glucose monitors, insulin pumps and even automated “closed-loop” systems that run on mobile apps to deliver insulin as-needed have radically changed the patient experience.

Sara Vasconcelos left), an assistant professor at U of T’s Institute of Biomedical Engineering, has worked with Cristina Nostro (right), an associate professor in the department of physiology, and her team in the McEwen Stem Cell Institute at UHN to extend the survival and functionality of pancreatic precursor cells generated from human stem cells.

Cell therapy could prove more liberating still.

University labs and biotechs are working on implantable devices that house insulin-producing cells derived from stem cells.

To that end, Cristina Nostro, an associate professor in the department of physiology in the Temerty Faculty of Medicine, and her team in the McEwen Stem Cell Institute at University Health Network recently discovered a more efficient way to generate and purify pancreatic precursor cells from human stem cells in the lab.

They have also found a way to vascularize those cells by working with Sara Vasconcelos, an assistant professor at U of T’s Institute of Biomedical Engineering. Together, they have extended the survival and functionality of the cells in animal models of diabetes.

The biggest problem with these therapies is that the immune system rejects them. The same challenge currently hinders pancreas and islet transplants.

“The immune system is an amazing machine, we’re lucky it’s so good,” says Nostro. “But it’s very difficult to control when it goes awry, as in autoimmune conditions.”

Nostro is working with immunologists at the university on a method to protect insulin-producing beta cells from immune rejection, and she says many researchers in the field are now focused on immune-protective approaches.

Another strategy for type 1 diabetes is to tamp down the autoimmune response before the disease progresses. The idea is to prevent immune cells that damage the pancreas while the body still produces beta cells.

“Groups around the world are bringing different ideas and creative approaches to treat type 1 diabetes, that’s the beauty of science,” says Nostro. “I am very hopeful about what the future holds. Who knows? Maybe we will see hybrid technologies combining a pump and cells. We have to keep an open mind.”

This story was originally published in U of T Med Magazine’s Insulin Issue.

'The future Bantings and Bests': How insulin's discovery at U of T is fuelling research 100 years later

Christopher.Sorensen — Fri, 19 Mar 2021 15:44:14 +0000

'The future Bantings and Bests': How insulin's discovery at U of T is fuelling research 100 years later

Christopher.Sorensen Fri, 03/19/2021 - 11:44

Cutline

U of T's Janet Rossant, pictured here in her SickKids lab, says a $25,000 grant from the Banting Research Foundation was a key moment early in her career (photo by Richard Lautens/Toronto Star via Getty Images)

Paul Fraumeni

Topic

Donnelly Centre for Cellular & Biomolecular Research

Banting & Best

Biochemistry

Hospital for Sick Children

Molecular Genetics

It was 1983 and Janet Rossant was 33 years old.

Six years earlier, she left her native England with degrees from Oxford and Cambridge. She had landed a position at Brock University in St. Catharines, Ont. – across the lake from Toronto.

Then an assistant professor of biology, Rossant headed a laboratory team seeking to understand how the embryo develops. To do that, the Rossant team was starting to develop transgenic mice.

“This was a new field of developmental biology, and we were excited by the possibility of being able to add genes to embryos and study their effect on development. But to do this research, we needed specialized equipment and we also needed the money to buy it,” says Rossant, who has been a researcher at the ��Ƶ for the past 36 years.

So, Rossant applied to the Banting Research Foundation (BRF), which awarded her $25,000 – not a huge amount, but an important influx of financing for a researcher who was starting to build a track record.

“People like to talk about the tipping point,” she says. “When you’re a young investigator and you don’t have a lot of funding, it’s hard to move to the next level. So, the Banting Foundation was then, and still is, a really important support for new investigators, providing that critical piece of funding just when you need it.”

That early support paid off for Rossant – and for global society.

By 1985, Rossant had moved to U of T and the Samuel Lunenfeld Research Institute (known today as the Lunenfeld-Tanenbaum Research Institute) at Mount Sinai Hospital.

Over the next 30 years, Rossant conducted research on genetics and stem cells that earned her renown and a bevy of awards. Today, Rossant is a University Professor in the department of molecular genetics at the Temerty Faculty of Medicine, a senior scientist and chief of research emeritus at the Hospital for Sick Children and the president and scientific director of the Gairdner Foundation.

It’s an impressive career arc that, in many ways, can be traced to the discovery of insulin at U of T decades earlier.

In 1921, sixty-three years before Rossant applied for that $25,000 fateful grant, an unlikely team was hard at work in a U of T lab on a disease – diabetes – that had killed millions over the centuries and continued to bewilder scientists.

Frederick Banting, a physician with little research experience, and Charles Best, a medical student, were investigating Banting’s plan to isolate the mysterious secretion of the pancreas that controlled metabolism.

J.J.R. Macleod, then U of T’s chair of physiology, somewhat reluctantly gave the team lab space, equipment and dogs to use for testing.

Banting’s idea worked.

The discovery won the Nobel Prize in 1923 and continues to enable people with type 1 diabetes to live full, rich lives – once an unthinkable outcome. But the legacy of insulin’s discovery goes well beyond diabetes by acting as a catalyst to stimulate a century of medical research in a dizzying array of areas.

For one thing, two research-supporting foundations were established in the spirit of Banting and Best, including the BRF.

“Our mission is to fund young investigators, the future Bantings and Bests, in the way they were funded by Macleod, at the beginnings of their careers when they have a bold idea that just might move society forward,” says Catharine Whiteside, BRF chair, former dean of medicine and an emerita professor with the department of medicine.

In 1960, W. Garfield Weston Foundation funding established the Dr. Charles H. Best Foundation. The original idea was to support research at the discretion of Best, who went on to conduct important studies in a number of areas and become a U of T research leader.

When Best retired in 1965, the funds were designated to U of T’s Banting and Best department of medical research. That unit later became part of the Donnelly Centre for Cellular and Biomolecular Research.

“Today, those funds are used to support researchers getting started on their careers through a program called the Dr. Charles H. Best Postdoctoral Fellows,” says Peter Lewis, the program’s board chair and former chair of the department of biochemistry at U of T. “This funding enables us to help researchers of a high calibre from around the world to pursue their ideas and to learn with the scientists of the Donnelly.”

These two foundations have helped launch remarkable careers.

“The influence of Banting and Best goes way beyond diabetes and insulin,” says Professor Reinhart Reithmeier, also a former chair of the department of biochemistry who was a winner of a Best Postdoctoral Fellowship in the late 1970s.

The Toronto insulin discovery continues to ignite important ideas from newer generations.

At the Donnelly Centre, the 2019 Best Postdoctoral Fellow Juline Poirson is studying the ubiquitin-proteasome system (UPS). It is critical in ensuring the normal functioning of cells, notably by destroying proteins that are no longer needed. But in diseases such as cancer, the UPS is dysregulated.

Poirson is working to understand why this happens with certain proteins. Her work could lead to important drug developments to treat diseases like cancer.

“I came from France to the Donnelly because I knew it would help me build on what I had already learned,” she says. “It is one of the best research centres in the world when you work on protein-protein interaction. This experience is going to help me for the rest of my career.”

Nomazulu Dlamini is an associate professor of pediatrics in the Temerty Faculty of Medicine and a staff physician at SickKids Hospital. The pediatric neurologist and scientist specializes in understanding and treating strokes in children. Her focus is dystonia, a disabling and painful disorder that can occur in children who have experienced a stroke. It’s characterized by involuntary, repetitive muscle contractions, twisting movements and abnormal posturing. Often, it is resistant to treatment.

It is thought that the problem originates in the basal ganglia, a network in the brain. Dlamini’s lab is studying the differences in the neural network between childhood stroke patients who have dystonia and those who don’t. Understanding why some children experience dystonia will increase the potential of developing effective therapies.

The BRF awarded Dlamini $25,000 in 2018 to support her work in understanding dystonia.

“That support has been very helpful. With the pilot data from the work we have been able to get because of the Banting funding, we’ve been able to leverage that for further funding,” says Dlamini.

“That’s all because Banting believed in our idea of discovering why there is this difference between these two groups of children.”

This story, which has been edited and condensed, was originally published in U of T Med Magazine’s Insulin Issue.

PBS Newshour commemorates U of T’s Charles Best, of insulin fame

wangyana — Fri, 05 Mar 2021 20:35:24 +0000

PBS Newshour commemorates U of T’s Charles Best, of insulin fame

wangyana Fri, 03/05/2021 - 15:35

Cutline

(Photo by Keystone-France/Gamma-Keystone via Getty Images)

Topic

Global Lens

The life of ��Ƶ’s Charles Best, who helped discover insulin, was recently commemorated in a PBS Newshour column in honour of Best’s birthday last month.

The piece recounts the story of how a winning coin toss gave Best the opportunity to work with Ontario surgeon Frederick Banting in a U of T laboratory. Best was only 21 years old and still a student at U of T at the time.

“The entire hot, sticky summer of 1921, Banting and Best toiled in a tiny, smelly laboratory, gathering their data,” PBS Newshour writes.

With the help of two other scientists, U of T graduate James Collip and J.J.R. Macleod, a U of T professor of biochemistry, Banting and Best isolated the pancreatic hormone, now known as insulin, that paved the way to lifesaving treatments for diabetes patients around the world, the column says.

It goes on to detail how, in 1922, a 14-year-old boy with end-stage juvenile diabetes became the first human to be treated with – and eventually saved by – insulin. While only Banting and Macleod were awarded the 1923 Nobel Prize in Medicine for the breakthrough, the column notes that Banting and Macleod shared their prize money with Best and Collip.

Insulin became “one of the most successful drugs of the 20th century,” PBS Newshour says.

Short exercise 'snacks' improve blood sugar regulation after meals, U of T study finds

Christopher.Sorensen — Thu, 10 Dec 2020 14:19:41 +0000

Short exercise 'snacks' improve blood sugar regulation after meals, U of T study finds

Christopher.Sorensen Thu, 12/10/2020 - 09:19

Cutline

A study by researchers in U of T's Faculty of Kinesiology and the Temerty Faculty of Medicine suggest brief bouts of chair stands or treadmill walking can reduce increases in post-meal insulin induced by too much sitting (photo by Andrey Popov)

Jelena Damjanovic

Topic

Faculty of Kinesiology & Physical Education

Whether you’re working from home or an office, the modern workday often involves spending hours sitting in front of a computer screen.

Not surprisingly, there’s a cost to such sedentary behaviour.

“Periods of prolonged sitting can be associated with elevated increases in the concentration of blood insulin, a hormone that regulates our blood sugar concentration following meals,” says Jenna Gillen, an assistant professor at the ��Ƶ’s Faculty of Kinesiology & Physical Education (KPE).

“While increased insulin following a meal is normal, exaggerated spikes in the hormone can be an early sign of risk for metabolic diseases, like type 2 diabetes, as it suggests the body is working harder to lower blood sugar concentration after meals.”

The good news is, we can do something about it and it involves snacking – on exercise.

Gillen worked with a team of researchers from KPE and the Temerty Faculty of Medicine to investigate whether breaking up periods of prolonged sitting with short exercise “snacks” could improve blood sugar regulation throughout the day in men and women. Recently published in the Journal of Applied Physiology, their findings suggest that interrupting sitting with brief bouts of repeated chair stands or treadmill walking can reduce increases in post-meal insulin induced by too much sitting.

The study found that interrupting eight hours of prolonged sitting every 30 minutes with one minute of repeated chair stands or two minutes of treadmill walks lowered insulin concentrations following lunch. Short walks have previously been shown to be effective, but this was the first study to demonstrate that body-weight resistance exercise, such as the repeated chair stands, are just as effective for improving glycemic control in adults who engage in prolonged periods of sitting, but are otherwise healthy.

“Importantly, repeated chair stands require no equipment or space beyond one’s sedentary area and may represent a practical strategy for mitigating cardiometabolic disease risk associated with prolonged periods of sitting,” says Gillen. “These findings are especially timely now when many individuals are looking for physical activity strategies that can be performed at home without the need for additional space or equipment.”

However, the researchers did not see a reduction in blood sugar concentrations throughout the day in response to the exercise snacks. This was surprising because studies in adults with obesity and/or impaired blood sugar regulation seen in type 2 diabetes have demonstrated that exercise snacks can lower post-meal spikes in blood sugar concentration. Gillen believes the explanation may lie in the fact that the participants of this study were relatively healthy with normal blood sugar concentrations.

“What this suggests is that exercise snacks in adults who engage in prolonged periods of sitting, but are otherwise healthy, are more likely to reduce the amount of insulin required to control blood sugar following a meal,” she says.

Gillen emphasizes that, while exercise snacks are beneficial to anyone who spends a lot of time sitting during the day, they should not be interpreted as a replacement for daily moderate-to-vigorous physical activity.

“That’s still very important,” she says.

Virtual symposium celebrates U of T’s discovery of insulin, looks to future of diabetes research

Christopher.Sorensen — Mon, 30 Nov 2020 22:03:15 +0000

Virtual symposium celebrates U of T’s discovery of insulin, looks to future of diabetes research

Christopher.Sorensen Mon, 11/30/2020 - 17:03

Cutline

Researchers and scholars discussed everything from the latest diabetes research to the socio-economic aspects of the disease at an online symposium presented by U of T (photo by vitapix via Getty Images)

Geoffrey Vendeville

Topic

Institute of Health Policy Management and Evaluation

Alumni

Dalla Lana School of Public Health

Meric Gertler