In marking the centenary of the discovery of insulin, we wanted to share some of the stories of researchers and clinicians whose pioneering work has advanced our understanding of insulin, islet biology, insulin resistance and diabetes.
Over the past century, the pursuit of “hormones of hormones” and the advancement of diabetes treatment has been filled with stories of cooperation, persistence, and triumph.
Cell Metabolism is one of the most widely used research journals in the world. It is the first time insulin has ever been discovered and the future of insulin is still promising.
Insulin: One of the greatest medical discoveries of all time
Guest Editor Tony K.T. Lam
If Tom Brady has cemented his place in the National Football League by making 10 Super Bowls in the past 30 years and winning his seventh individual Super Bowl,
The discovery of insulin 100 years ago in the physiology department of the University of Toronto is undoubtedly one of the greatest medical studies (if not just one) in history.
Just at the University of Toronto in 1921, Banting, Best, Collip, and MacLeod succeeded in extracting and purifying insulin, which was injected to lower blood sugar levels in diabetic dogs.
Soon after, researchers found that insulin injections lowered blood sugar levels in people with type 1 diabetes.
Needless to say, insulin is consistent and reproducible in lowering blood sugar levels in all species, male and female, regardless of whether they have type 1 diabetes, and it is also applicable to all species with type 2 diabetes.
After graduating as an undergraduate in 1998, I began studying the role of insulin in muscle and liver under the direction of Drs. Amira Klip and Adria Giacca in the Department of Physiology at the University of Toronto.
My research was funded with summer and postgraduate fellowships from the Banting and Best Diabetes Centre.
Adria was a postdoctoral fellow with the late Dr. Mladen Vranic, who was the last postdoctoral fellow at Dr. Best.
Over the past 40 years, in collaboration with Dr. Gary Lewis, now director of the Banting and Best Diabetes Center, and Amira, they have diligently studied how insulin affects glucose uptake in muscle and fat, as well as glucose production in cells, rats, mice, dogs, and humans.
Then I went to New York City to do postdoctoral research with Dr. Luciano Rossetti, exploring the role of insulin in the brain, and I began to meet scientists around the world, including Dr. Barbara Kahn, who, with Amira, had spent the past 40 years at Harvard studying the role of insulin in fat and muscle.
In 2006, I returned to the Toronto General Hospital Research Institute to set up my own lab.
It was there that I met Gary and other dedicated researchers, such as Drs. Bernie Zinman, Dan Drucker, and Pat Brubaker, who had explored the role of insulin and GLP-1 in cells, rodents, and humans, and whose findings, along with many other studies around the world,
It’s a field that has grown tremendously over the last 40 or 50 years.
To mark the 100th anniversary of the discovery of insulin, I have collaborated with the editors of Cell Metabolism to produce this special issue.
In addition to reviews and opinion articles, this special issue presents a timeline on the history of insulin and diabetes.
In addition, we share the personal stories of 18 scientists in the field who review the significance of insulin discovery and offer their views on the future of insulin research.
These reviews and research articles, written by dedicated women and men, mark 40 or 50 years of research into the role and secretion of insulin. Even if today’s readers can peruse these articles in detail, the impact of insulin’s discovery 100 years ago on the human body is beyond simple description.
The success of insulin in treating diabetes is beyond doubt.
In terms of my personal experience, found that insulin had a profound impact in the 100 years later, the university of Toronto team valuable legacy by banting and best diabetes center funded empowerment and plan recognition, many researchers all over the world to advance wave upon wave for the study of insulin and diabetes has dedicated his life, made great contribution to science existing understanding…
In my opinion, these are solid proof that the discovery of insulin is the GOAT of medical research.
One final point: While my story is unique to me, with 100 years of history as witness, my experience in Toronto is not unique.
I’m pretty sure that if you simply ask former postdocs and/or graduate students in Drucker’s lab in Toronto, they can more or less describe a similar rich experience.
As Roundup, Voices and Original Research articles in this issue note, we as researchers in the field of diabetes, obesity and metabolism have a lot to learn in the next 100 years.
Maybe history will repeat itself and another GOAT will appear in this field.
Time will tell what Tom Brady’s legacy will be 100 years from now.
Director of the Diabetes Research Laboratory at Northwell Medical Center
Expect to celebrate insulin
In the early 19th century, a wide range of endocrine-like systems was gradually discovered, paving the way for the discovery by Minkowski and von Mehring of the mechanism by which pancreatectomy produces hyperglycemia.
The pancreas, implanted in the abdomen and elsewhere, successfully controls blood sugar, mimicking an endogenous endocrine biological system.
For the next three decades, teams of researchers in Europe and North America worked fairly close to success in their quest to extract bioactive peptides from the pancreas.
Banting and Best, using Macleod’s formula and machinery at the University of Toronto, succeeded in producing extracts that are active in animals, but not in humans.
Another team at the University of Toronto, led by Kripp (who works in McLeod’s lab), was the first to successfully produce insulin on a large scale that can be safely used in patients with hyperglycemia.
In partnership with the pharmaceutical company Eli Lilly, they have scaled up production to meet worldwide demand.
The medical community rushed to conclude that Type 1 diabetes was under control and treatable.
In the decades that followed, the diabetes research community came to realize that insulin replacement therapy could not prevent blindness, kidney failure and shortened life in many people with type 1 diabetes, who were insulin-deficient.
The festivities celebrating the discovery of insulin in Toronto 50 and 25 years ago were limited because existing treatments for Type 1 diabetes were not yet able to prevent the disease’s devastating effects.
Today, blood sugar monitors, insulin pumps, retinal laser therapy and other treatments finally offer patients a promising path to a full, fruitful life.
But there is a great irony: the ongoing COVID-19 pandemic is killing patients and caregivers around the world, preventing us from celebrating the 100th anniversary of insulin with a sense of comfort.
Nevertheless, let’s look forward to the opportunity to celebrate the challenge of COVID-19 in the near future, so that we can sincerely and appropriately celebrate the conquest of Type 1 diabetes.
Sonia M. Najjar
A journey of scientific discovery of the role of insulin in lipogenesis
If we look at the before-and-after photos of the first insulin patients, there are a number of striking features. The most striking is that they were very thin before the treatment, but after the treatment they became what we would call “dramatically overweight.”
The relationship between insulin and adipogenesis remains a puzzle.
Together with other scientists, I have been trying to map the role of insulin in regulating hepatic steatosis.
We soon learned that after docking with the plasma membrane of a hepatocyte via its receptor, the insulin/receptor complex is chaperonated by CEACAM1 and enters the degradation pathway for clearance.
During this process, CeACAM1 detaches from the complex and binds to fatty acid synthase (FASN) to inhibit its activity and limit new fat generation.
These activities are closely related to the impulsive release of insulin in the portal vein, so physiological portal hyperinsulinemia will induce the expressions of CEACAM1 and FASN in liver cells, while the acute impulsive release of insulin will cause the phosphorylation of CEACAM1, which is necessary to mediate insulin clearance and inhibit FASN activity.
In recent years, hepatic steatosis has been increasingly identified as a mechanism for the development of chronic liver disease, and its association with hyperinsulinemia/insulin resistance has been questioned, and our findings contribute to the discussion.
These observations were first published in Cell Metabolism in 2005, and this was the first manuscript in the journal.
However, we cannot say for sure that this work will lead to a way to balance lipogenesis and glucose production in the liver, or whether insulin resistance is the same as insulin’s inability to inhibit lipogenesis and glucose production in the liver.
Tiger Gate Hospital, Tokyo, Japan
Another 100-year harvest in insulin research
One of the most fulfilling moments in my medical career was witnessing a type 1 diabetic recover, like a miracle, from high blood sugar, excessive weight loss, and general weakness with just a single injection of insulin.
Similarly, in the nearly 100 years since its discovery, insulin has saved tens of millions of lives worldwide.
Study of insulin targets initially limited to skeletal muscle, liver, and fat cells, but now has extended to islet B cells, brain and blood vessels, and the recent research of macrophages and gut, so people bosom expectation, hope for the further study of the various organs to uncover the mysteries of these pathways in the end.
Enteroglycin or adiponectin – adiponectin receptor (Adipor) is just one example of many endocrine and nervous systems that are involved in the fine regulation of the insulin-insulin receptor (IR) system.
Insulin is appropriately called the “hormone of hormones,” and the insulin-IR system, which is regulated by upstream neural networks and peripheral organ systems, can be likened to the “chief orchestra” rather than the “conductor,” coordinating the complex mechanisms that maintain the body’s homeostasis.
In my opinion, the whole significance of insulin research is that IR in multiple organs not only holds the key to metabolic regulation, including glucose, fatty acid, ketone body and amino acid metabolism regulation, but also plays a central role in the regulation of complex inter-organ interactions.
There is no doubt that insulin research will prove to be a more fruitful and exciting field than it has been for the past 100 years, and its fruitful results will yield valuable insights into human health and disease and its mechanisms.
Michael P. Czech
University of Massachusetts Medical School
I feel privileged to study insulin
The upsurge of research on insulin and its effects occurred during the period from 1975 to 1985.
During this period, knowledge expanded from measuring insulin’s binding to its mysterious membrane receptor to its cDNA cloning — narrowing the vast research gap.
In the midst of this mania, on a bright afternoon in 1978, Paul Pilch of the Czech Laboratory at Brown University held up an autoradiography photograph of his experiment – and we were delighted to see a single, distinct dark band appear against a perfectly clear background.
Over the next two years, Joan Massague, Paul, and the rest of our group used this technique to correctly infer the isotetramer subunit structure of the insulin receptor and to obtain a similar structure of the IGF1 receptor.
We published a paper in 1980 in PNAS that named two receptor subunits A and B, a designation that has persisted to the present day.
This is an exciting and exciting finding that has put a smile on the faces of all the researchers who were involved in the study 40 years ago.
I deeply feel, as a scientist is how honored ah!
Despite many successes like this in hundreds of laboratories, the need to translate basic research findings into clinical applications for diabetes has never been greater.
Combining powerful technologies through research efforts is our goal now.
We are combining the Corvera lab’s technology to generate large numbers of human adipose tissue stem cells with the CRISPR-based approach from the Czech lab to further enhance the therapeutic potential of insulin.
The question we wanted to explore was: can metabolic diseases be treated by cell therapy?
We recently showed that inserting a CRISPR-enhanced “hyperpowered” human fat cells into mice that had been genetically modified by humans lowered blood sugar more than ungenetically modified fat cells.
Indeed, being a scientist makes me feel honored!
Barbara E. Corkey
Boston University School of Medicine
The saga of the insulin molecule continues
The 100th anniversary of the discovery of insulin, a rare molecule, is being celebrated around the world, and it will continue to challenge and inspire humanity.
I was fortunate enough to take part in the 50th anniversary commemoration in Jerusalem, and the 100th anniversary commemoration, which is being celebrated remotely during the pandemic.
There were many important milestones in the discovery of insulin and its impact over the course of 100 years, including the treatment of diabetes;
Determination of insulin structure, synthesis and analysis;
The physiology of insulin action, including receptor interactions;
And the physiological and pathophysiological roles of insulin in energy supply and storage.
By the next anniversary, we expect to build on the current frontiers of science to have a much deeper understanding of insulin’s role in several important areas :(1) obesity and related disorders, with an emphasis on the role of the brain in the development of obesity;
(2) The mechanism of fasting insulin elevation and its effect on the development of diabetes mellitus, cancer and fatty liver;
(3) the mechanism of insulin resistance and determine whether it is harmful.
Insulin is a rare molecule, perhaps unique.
For most living people, insulin may affect their health and well-being at some point in their lives, which has been linked to many common causes, including obesity, cardiovascular disease, diabetes, cancer, fatty liver and polycystic ovary syndrome.
Insulin will continue to inspire and challenge us.
Mark A. Atkinson
University of Florida
Dream of insulin
In 1921, the discovery of a way to purify insulin from an animal’s pancreas changed the course of insulin-dependent diabetes.
The treatment, while not perfect, offers hope.
Before that, children often comatose and die from diabetic ketoacidosis — more than 50 children crammed into hospital wards as grieving family members waited for their inevitable death.
In January 1922, Leonard Thompson’s groundbreaking treatment set the course for a change in the disease that would last nearly 100 years.
In fact, there have been tremendous advances in insulin therapy over the past century, in terms of delivery methods, treatment forms, and packaging.
While it is never a good thing to have insulin-dependent diabetes, now is the right time, if one is destined to develop the disease, and for many (but not all) sufferers, the future holds promise.
Unfortunately, due to the obstacles, such as cost, insurance, government/public health policies, lack of education, the so-called pharmacy benefit managers, retail price, poor stability of insulin/lack of refrigeration equipment, etc., in the developing countries and developed countries, there are still many patients are suffering, even to death, as of 1921.
Let us pray that the dream of the inventor of insulin will be realized as soon as possible, and that it will be met for all who need it.