Banting &amp; Best

Myhal Centre for Engineering Innovation & Entrepreneurship

Toronto General Hospital

One hundred years ago this month, scientists at the �ؿ�ζSM and its partner hospitals carried out the first studies that demonstrated the ability of insulin to lower blood sugar levels in animals and prevent their death from diabetes.

Three months later, insulin was successfully administered to a person with type 1 diabetes at Toronto General Hospital. His life would become the first of millions around the world to be saved by insulin – one of the landmark medical discoveries of the 20^th century.

On Friday, the historical significance of the discovery was marked by the unveiling of a commemorative bronze plaque at a ceremony hosted by Parks Canada and the Historic Sites and Monuments Board of Canada (HSMBC) at the Myhal Centre for Engineering Innovation & Entrepreneurship on U of T’s St. George campus.

The event was attended by government dignitaries including Sonia Sidhu, member of parliament for Brampton South. The final location of the plaque, which is inscribed by bilingual text, will be determined at a later date.

“The story of insulin is a brilliant example of the power of collaboration – in this case, how a university, its hospital partners and a pharmaceutical company could work together and change the world,” said Christine Allen, U of T’s associate vice-president and vice-provost, strategic initiatives.

“On this illustrious foundation, U of T and its hospital and industry partners built a culture of discovery, innovation and collaboration that has transformed health care and continues to have a ripple effect worldwide.

From left: Patricia Brubaker, Richard Alway, Sonia Sidhu, Christine Allen, Christine Loth-Brown and Lynn Wilson (photo by Johnny Guatto)

The ceremony marked the culmination of Insulin 100, a year-long campaign to mark the centenary of insulin’s discovery and celebrate a legacy of health innovation that continues to be advanced by U of T and its partner hospitals, research institutes and industry partners.

“The Parks Canada plaque not only serves as a fitting reminder of the critical research discoveries made here at U of T – it will also inspire future trainees and researchers whose work will be pivotal in the health research discoveries made over the next hundred years,” Allen said.

Patricia Brubaker, a professor in the departments of physiology and medicine at the Temerty Faculty of Medicine and member of the faculty’s Banting & Best Diabetes Centre, described the key areas of diabetes research being investigated by U of T faculty and students today.

“Our interests cover the spectrum of diabetes research, including not only type 1 diabetes, but also type 2 diabetes, which is now reaching epidemic levels, affecting one in six Canadians, as well as gestational diabetes or diabetes during pregnancy,” said Brubaker, who has been conducting diabetes research for four decades.

“We are studying the causes of diabetes through research into obesity, a major risk factor for type 2 diabetes; we are interrogating new approaches to the treatment of diabetes, including stem cell replacement therapy and new pharmacologic treatments; and our researchers are exploring the fundamental mechanisms that underlie the normal regulation of glucose and fat metabolism and how this is disrupted in diabetes, leading to long-term complications such as kidney and cardiovascular disease.”

Brubaker also reflected on the impact of insulin and diabetes research on her own life. As a person living with type 1 diabetes, she noted she is “one of legions who would not be alive today without the discovery of insulin.”

In addition to saving countless lives, the discovery of insulin helped establish U of T, its partner hospitals and Toronto more generally as a vanguard of diabetes research and treatment.

In April, some of the latest developments in the field were discussed at the Insulin100 conference, a two-day virtual symposium that drew over 6,000 attendees from around the world.

Also in April, U of T’s Banting & Best Diabetes Centre and Diabetes Action Canada hosted “100 Years of Insulin – Celebrating its Impact on our Lives,” a public celebration and forum featuring an array of topics of interest to people living with diabetes.

It was at this public celebration that Canada Post unveiled a special stamp to commemorate the discovery of insulin. The stamp, which depicts a vial of insulin resting on an excerpt from Banting’s unpublished memoirs, was unveiled from the Banting House National Historic Site of Canada in London, Ont. – in the very room where Banting first got the idea that eventually led to the discovery of insulin. Brubaker and Scott Heximer, chair of the department of physiology at the Temerty Faculty of Medicine and a principal investigator at the Ted Rogers Centre for Heart Research, worked with Canada Post and Banting House to ensure the stamp’s historical accuracy and help source archival material.

The stamp would be the first of several commemorations to mark the place of insulin in the cultural tapestry of Canada’s heritage.

In May, Historica Canada released a Heritage Minutes segment paying tribute to the discovery. The segment depicts the plight of 13-year-old diabetes patient Leonard Thompson, and the efforts of Banting and Best to formulate and refine the insulin treatment that ultimately saves Thompson’s life. Again, experts from U of T – including science and medicine librarian Alexandra Carter, archivist Natalya Rattan and medical historian Christopher Rutty – were consulted on the project to ensure historical accuracy.

In July, the Royal Canadian Mint issued its own commemoration in the form of a two-dollar coin depicting a monomer (a building block of the insulin molecule), insulin cells, blood cells, glucose and the scientific instruments used in early formulations of insulin.

The importance of insulin was recognized almost immediately after its initial discovery. In 1923, the Nobel Prize in Physiology or Medicine was awarded to Frederick Banting and James McLeod, who isolated insulin in U of T’s department of physiology. The prize was shared with physiology and biochemistry student Charles Best and biochemist James Collip.

U of T researchers continue to be recognized for their stellar work in advancing diabetes research.

Brubaker was honoured last year with a Lifetime Achievement Award from Diabetes Canada, a recognition of her longstanding contribution to diabetes research and the Canadian diabetes community. And, earlier this year, Daniel Drucker, professor of medicine in the Temerty Faculty of Medicine and a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health, was awarded a Canada Gairdner International Award for research on glucagon-like peptides that has helped revolutionize treatments for type 2 diabetes – an honour he shared with collaborators at Harvard University and the University of Copenhagen.

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

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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 �ؿ�ζSM’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 �ؿ�ζSM 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.”

U of T scientist receives Gairdner International Award for metabolism research

Christopher.Sorensen — Wed, 07 Apr 2021 19:20:24 +0000

U of T scientist receives Gairdner International Award for metabolism research

Christopher.Sorensen Wed, 04/07/2021 - 15:20

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U of T's Daniel Drucker has been jointly awarded the Canada Gairdner International Award for research on glucagon-like peptides – hormones that emanate from the gut to control insulin and glucagon to balance the body's blood sugar (photo by Johnny Guatto)

Jim Oldfield

Topic

Lunenfeld-Tanenbaum Research Institute

Mount Sinai Hospital

University Health Network

A scientist at the �ؿ�ζSM has been jointly awarded a 2021 Canada Gairdner International Award for research that has helped revolutionize treatments for type 2 diabetes, obesity and intestinal disorders.

Daniel Drucker receives the honour with Joel Habener of Harvard University and Massachusetts General Hospital, and Jens Juul Holst of the University of Copenhagen, for research on glucagon-like peptides – hormones that emanate from the gut to control insulin and glucagon, which work in tandem to balance sugar levels throughout the body.

The award comes as U of T celebrates the 100th anniversary of the discovery of insulin, a finding that paved the way for a century of ground-breaking research at the university and its partner hospitals – and just a week before the Insulin100 global symposium.

“I am extremely excited and honoured that the Gairdner Foundation has recognized our collective work on the glucagon-like peptides, and its translational importance for the treatment of metabolic disorders," said Drucker, a professor in the department of medicine at the Temerty Faculty of Medicine and a senior scientist at the Lunenfeld-Tanenbaum Research Institute at Sinai Health.

“I am also very grateful for the dozens of contributions made by so many talented trainees that I have been privileged to work with at the �ؿ�ζSM.”

Working both independently and collaboratively over more than four decades, Holst, Habener and Drucker discovered the peptides known as GLP-1 and GLP-2, detailed their molecular and physiological effects in cells and animals and translated those findings in human studies that have led to several new classes of drugs.

Medications based on GLP-1 have begun to significantly improve the care of people living with type 2 diabetes and obesity – conditions that have historically suffered from few or suboptimal treatments. More than 100 million people with type 2 diabetes have been treated with a GLP-1 analogue or a DPP-4 inhibitor, a class of drugs that prevents the breakdown of GLP-1 and GLP-2 and thereby helps improve blood sugar control.

Drugs based on GLP-2, meanwhile, can improve nutrient absorption in people with short-bowel syndrome, eliminating the need for intravenous feeding in some patients. And GLP-1-based peptides show promise as cardio-protective agents and in non-alcoholic fatty liver disease and neurodegenerative disorders.

“GLP-1 therapies have really advanced our treatment for diabetes and metabolic disorders, and GLP-2 can effectively address a huge unmet need in people with intestinal failure,” said Drucker, who will give an overview of his work at the Insulin100 symposium “Let’s see what more they can do.”

The Gairdner Foundation was established in 1957 to recognize fundamental research that impacts human health, bestowing 395 awards to scientists from 35 countries. About a quarter of those recipients have later received Nobel Prizes.

The foundation increasingly honours recipients jointly in recognition of the collaborative nature of scientific research and with an eye on human impact, which may only become clear over decades.

The scientific journey from the discovery of glucagon-like peptides to their application in several diseases is indeed one of incremental and cumulative change.

Holst made the initial observation that patients who had undergone intestinal surgery experienced a rise in insulin followed by a drop in blood sugar after eating – an early sign of links between the gut, sugar levels and the pancreas, which is the main site of insulin and glucagon production.

Holst later identified a type of glucagon in blood that originated in the gut but was different from glucagon made in the pancreas.

Habener began work around the same time that led to the discovery of glucagon-like peptides. He used pancreatic cells from monkfish to show that glucagon and another hormone were genetically encoded in those cells as larger, precursor hormones.

He later found that a precursor called proglucagon included amino acid sequences for two related hormones, and through further work in mammals characterized these peptides – now known as GLP-1 and GLP-2.

Drucker joined Habener’s lab as a post-doctoral researcher in the mid-1980s and helped detail the biological function and systemic effects of the peptides. The scientists later observed that gut cells release GLP-1 into the blood in response to food – increasing insulin release in the pancreas and tempering glucagon, and also slowing digestion and decreasing appetite.

The results suggested that boosting GLP-1 might improve the glucose-dependent release of insulin in people with type 2 diabetes. Clinical tests by Holst and others confirmed this suspicion and led to drugs known as GLP-1 agonists, now a staple in type 2 diabetes management.

Drucker then further detailed the workings of GLP-2, which also arises in the gut as a response to food. He showed, in collaboration with Patricia Brubaker in U of T’s department of physiology and department of medicine, that the main role of GLP-2 is to support the growth and health of intestinal cells that enable food absorption. This led to a new treatment for short-bowel syndrome.

Drucker also uncovered the workings of GLP-1 in the brain and heart, as well as the circulatory and immune systems, opening new lines of investigation. His work, together with findings from Holst and others, also led directly to the development of dipeptidyl peptidase-4 (DPP-4) inhibitors.

Drucker attributes much of his success to a focus on research questions with medical relevance, which he said followed naturally from his education as a physician and may have helped compensate for his relatively scant training in the basic sciences.

“Many scientists are better trained, but I’ve always kept one eye on unmet clinical needs and chosen research experiments accordingly,” said Drucker, who counts other clinician-scientists such as Habener – and former U of T department of medicine chairs Charles Hollenberg and Gerard Burrow – as key mentors.

Drucker also acknowledges the research contributions of his many trainees and colleagues, as well as some good fortune – including his arrival in Boston just as Habener’s lab shifted focus from thyroid function to glucagon.

Gary Lewis, director of the Banting and Best Diabetes Centre at U of T and a physician-scientist, has known Drucker for three decades and highlights his methodical approach to research.

“Dan understands better than most that true scientific advances are a marathon, not a sprint,” said Lewis, who is a professor in the departments of medicine and physiology at the Temerty Faculty of Medicine and an endocrinologist at University Health Network.

“He has contributed decades of careful work, with a precision in controls and other aspects of the experimental process that few have. This is not work that made a quickly forgotten splash in high-profile journals, but it underpins the durable impact for which he is now being rewarded.”

Lewis also cites scientific integrity, or the unbiased testing of hypotheses, as key to Drucker’s work.

“Too many scientists are enthralled with the ideas behind their hypotheses, but Dan is resolute in letting the data speak.”

Lewis said Drucker brings an uncommon work ethic to both his research and pursuits outside the lab – an intensity that has yielded a breadth of knowledge in work with industry on effective treatments for patients.

“He is simply one of the greatest scientists this country has ever produced,” he said.

Trevor Young, dean of U of T’s Temerty Faculty of Medicine and a clinician-scientist, said the work by Holst, Habener and Drucker is a classic tale of scientific inquiry that runs from the bedside to the lab bench and back to patients.

“I’m reminded of insulin, and the drivers and mechanics of that discovery,” said Young. “This is a story of pursuit and perseverance, but also of measured observation and collaboration at many steps along the way. And it’s changing millions of lives.”

Diabetes disparities: U of T researchers work with communities at risk

lanthierj — Mon, 05 Apr 2021 12:58:31 +0000

Diabetes disparities: U of T researchers work with communities at risk

lanthierj Mon, 04/05/2021 - 08:58

Cutline

(Photo by iStockPhoto/Getty Images)

Topic

Breaking Research

Dalla Lana School of Public Health

Indigenous

Rick Bhurji was shocked to learn that, at age 47, he had type 2 diabetes.

His next thought was: What did I do wrong?

Rick’s daughter, Anjali, noticed that many of their Indo-Canadian friends and family had “mysteriously” developed diabetes. She figured her father’s diabetes was due to his love of pop and junk food.

“For many of us who are South Asians, we internalize and blame ourselves for the diabetes epidemic in our community, but that is really unfair,” says Ananya Banerjee, an assistant professor at the �ؿ�ζSM’s Dalla Lana School of Public Health and a researcher with the Temerty Faculty of Medicine’s Banting & Best Diabetes Centre.

In fact, people from communities of colour across Canada are at higher risk for diabetes. The incidence rate of type 2 diabetes is double in Black communities and triple in South Asian and First Nations communities, compared to white Canadians.

A recent report found that First Nations children in Manitoba are 25 times more likely to be diagnosed with type 2 diabetes than other children. But disparities in diabetes are about more than ethnicity.

Researchers have found that location, income level, education, mental health, and experiences of racism and trauma can all profoundly impact the development and progression of diabetes.

By looking beyond basic biology, health-care providers are not only identifying which communities are at risk for diabetes, but also what interventions can make a difference.

“In health care, we tend to take a one-size-fits-all approach,” says Aisha Lofters, a clinician scientist and an associate professor of family and community medicine at the Temerty Faculty of Medicine.

Lofters is also co-leader of the BETTER WISE project which aims to improve the screening and prevention of cancer and chronic illnesses, including diabetes.

In practice, set guidelines and flowsheets don’t work for all individuals, explains Lofters.

Rather than “wagging the finger” at a patient who, for instance, isn’t meeting the recommended amount of exercise, the BETTER WISE project works with the patient to set individualized, attainable goals – such as going for a 15-minute walk each week.

Banerjee took a similar approach with the South Asian Adolescent Diabetes Awareness Program (SAADAP), providing education and prevention strategies to 80 South Asian teens with a family history of diabetes.

Through this pilot program, about eight in 10 participants reduced their intake of sweets and junk food and encouraged their family members to eat healthier.

Anjali and Rick, for instance, learned recipes for a healthy mango lassi and chickpea salad that have become staples in their home.

Outcomes of tailored diabetes programs are promising but, as obesity management expert and U of T alumnus Sean Wharton explains, they point to larger flaws in Canada’s health-care system.

“Disparity has come about because of a health-care system that isn’t serving people of colour,” says Wharton.

Beyond adjusting care to fit individual patient needs, he says some of the most effective ways of treating disparities in diabetes are at the grassroots level, such as in places of worship and community centres.

“These are spaces where the people working with the community are not biased against them, and they’re not blaming and shaming them, making them feel unrecognized or discriminated against,” explains Wharton.

In an effort to dispel internalized blame or stigma related to diabetes, Banerjee, through SAADAP, highlights the social determinants of health, such as the walkability of neighbourhoods and the burden of precarious employment, and how they affect the participants’ health.

Those lessons made Anjali realize, “There’s no need to feel horrible, and that you caused this, because you didn’t.”

Recent findings from the Manitoba Centre for Health Policy and the First Nations Health and Social Secretariat of Manitoba (FNHSSM) showed that First Nations individuals access primary care at a similar rate to others in the province. However, that care is not reducing complications from type 2 diabetes, such as amputations and kidney failure.

“The health system has made it the responsibility of the client with this simplistic idea that if you live healthy, eat healthy and exercise, you’re less likely to have type 2 diabetes. We know there’s more to it than that,” says Lorraine McLeod, associate director of the Diabetes Integration Project (DIP), a mobile program that First Nations leaders support to provide on-reserve diabetes care and treatment to more than a dozen First Nations communities in Manitoba.

Programs such as the centre’s DIP, B.C.’s Diabetes and My Nation and the cross-Canada FORGE AHEAD program have made significant improvements in diabetes prevention and management by being created by or developed in partnership with First Nations communities.

Since the late ’90s in Manitoba, First Nations leaders have been calling for action and collecting the necessary data to address the growing epidemic of diabetes in Indigenous communities.

“Oftentimes, research has been led by non-Indigenous researchers who have used their voice and academic lens to analyze Indigenous people, which often leads to continued stigmatization, and upholds the colonial practices and policies that were put in place to assimilate First Nations, Métis and Inuit people into Canadian society,” says Leona Star, the centre’s director of research.

As an example of a dataset that accurately identifies First Nations according to their own indicators of well-being, Star points to the national Regional Health Survey (RHS), which she says was “designed and delivered by First Nations with our cultural framework and code of ethics.”

According to Star, RHS data has led to federal funding for multiple Indigenous health initiatives, including diabetes prevention. While Star emphasizes the need for First Nations people to govern their own information and data, known as “data sovereignty,” she calls for more action.

“It is also important to look at the effectiveness and impacts of research findings,” says Star. “Although significant investments have been made to undertake research around diabetes, the rates of diabetes continue to increase and climb especially amongst First Nations.”

While evidence led or co-led by First Nations is available, she says what is lacking are policies and implementation recommendations to address discrimination and disparities in health care.

Wharton says the key question is why researchers and health-care providers aren’t acting on what they already know.

To address the disparities created by bias, racism and systemic inequalities, he says it’s time that practitioners embrace the strengths of Indigenous peoples and people of colour, rather than assessing how these patients adhere to a system that wasn’t designed for or by them.

“We need to shake the foundations of how we help,” he says.

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

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

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(Photo by Getty Images/iStockphoto)

Jim Oldfield

Topic

Institute of Biomedical Engineering

Faculty of Applied Science & Engineering

Insulin

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 �ؿ�ζSM’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.

Event to mark 100th anniversary of U of T's discovery of insulin and map future of diabetes care

Christopher.Sorensen — Fri, 26 Mar 2021 13:21:31 +0000

Event to mark 100th anniversary of U of T's discovery of insulin and map future of diabetes care

Christopher.Sorensen Fri, 03/26/2021 - 09:21

Cutline

(Photo by Samara Heisz/Getty Images)

Topic

Mount Sinai Hospital

Sir Frederick Banting

St. Michael's Hospital

The �ؿ�ζSM will co-host a public celebration this spring on the impact of insulin, one of several Insulin100 events that will mark the centenary year of a discovery that has saved the lives of millions of people.

On April 14, 100 Years of Insulin: Celebrating Its Impact on Our Lives will feature researchers sharing developments in diabetes care and people with diabetes who are patient partners with Diabetes Action Canada.

Bruce Perkins, a diabetes researcher who lives with type 1 diabetes, will speak about the rapid evolution of treatments, including insulin pumps, continuous glucose monitors, islet transplants and stem cells.

“It is humbling to realize what an extraordinary thing this discovery was 100 years ago, and that we’re so fortunate to be able to celebrate it in its fullest,” said Perkins, a professor in U of T’s Temerty Faculty of Medicine and director of the Leadership Sinai Diabetes Centre at Sinai Health. “The history really motivates me. It was a simple discovery with so much impact.”

Diabetes Action Canada will present the event in collaboration with the Banting & Best Diabetes Centre (BBDC) at U of T and the Temerty Faculty of Medicine’s department of medicine. The Division of the Vice-President, Research and Innovation at U of T will also support the event along with Diabetes Canada and the JDRF Canada, a non-profit focused on type 1 diabetes research and advocacy.

Grant Maltman, curator at the Banting House National Historic Site of Canada, will recount Frederick Banting’s middle-of-the-night moment that changed history. He will also unveil a Canada Post stamp commemorating the 100th anniversary of the discovery.

Alice Cheng, an associate professor in Temerty Medicine’s department of medicine and an endocrinologist at Trillium Health Partners and Unity Health Toronto, will co-host a panel on diabetes treatments.

“It’s exciting to learn from the past in terms of understanding the history of the discovery, and then learn about what’s happening now and what might happen in the future,” Cheng said. “It is a celebration of the achievement, but also meant to further inspire everyone to continue this work so things keep getting better. It’s a very proud moment.”

People living with diabetes will be front and centre at the event. They include:

Mike Alexander, an Anishinaabe artist and athlete who has struggled with depression and addiction. He is a Sixties Scoop survivor and recently became a member of Diabetes Action Canada’s Indigenous Patient Circle.
Chloe Pow, who was diagnosed with diabetes at the age of four. She has become an advocate for people living with diabetes and, together with her father Conrad Pow, provides volunteer peer-support for other children who have been recently diagnosed.
Jen Hanson, the executive director of the non-profit Connected in Motion. She has lived with type 1 diabetes for more than 30 years and will share ways to lead an active and healthy life.

As well, researchers from across Canada will explain how people living with diabetes have begun playing an active and vital role in research studies.

“When we started to explore how to celebrate this milestone, we knew that people living with diabetes needed to be at the heart of it,” said Gary Lewis, director of the BBDC and scientific co-lead for Diabetes Action Canada.

“We are so thrilled to have an array of speakers who will be sharing their experiences in a way that will educate and inspire,” said Lewis, who is a professor in the department of medicine in the Temerty Faculty of Medicine.

“Our greatest hope is that a cure will happen within the next 100 years, but for now we want to show our appreciation for this life-saving discovery.”

'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

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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

Hospital for Sick Children

Biochemistry

Insulin

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 �ؿ�ζSM 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 �ؿ�ζSM’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.

‘Our very first biotech win’: How U of T’s discovery of insulin made it a research and innovation powerhouse

rahul.kalvapalle — Wed, 04 Nov 2020 17:05:12 +0000

‘Our very first biotech win’: How U of T’s discovery of insulin made it a research and innovation powerhouse

rahul.kalvapalle Wed, 11/04/2020 - 12:05

Cutline

U of T's Patricia Brubaker, who has spent nearly 40 years studying anti-diabetic gut hormones, says the future of diabetes research will be figuring out how to prevent the disease in the first place (photo by Johnny Guatto)

Rahul Kalvapalle

Topic

Institute of Biomedical Engineering

Faculty of Applied Science & Engineering

Entrepreneneurship

Health Innovation Hub

Insulin