Insulin: A GOAT of medical discovery
Authors: Tony K.T. Lam
Journal: Cell Metabolism (2021)

If Tom Brady winning his 7th Super Bowl over 10 tries in the past 3 decades has cemented himself as the undeniable GOAT (greatest of all time) in the National Football League, then the discovery of insulin made in the Department of Physiology at the University of Toronto 100 years ago is no doubt one of the greatest (if not the greatest) of all time in medical research. It was here that Drs. Banting, Best, Collip, and Macleod successfully extracted and purified insulin, and lowered glucose levels in dogs with diabetes via insulin injection in 1921. Soon after, insulin injection was found to lower blood glucose levels in patients with type 1 diabetes. The consistence and the reproducible success in lowering glucose levels by insulin across all species in both females and males with or without type 1 diabetes, as well as the ability of insulin to lower blood glucose levels across all species with type 2 diabetes, are undeniable. After finishing undergraduate studies in 1998, I began studying insulin action in muscle and liver under the supervision of Drs. Amira Klip and Adria Giacca in the Department of Physiology at the University of Toronto, and my studies were sponsored by the Banting and Best Diabetes Centre summer and graduate studentship, respectively. Adria was a postdoctoral fellow of the late Dr. Mladen Vranic, who was the final postdoc of Dr. Best. Together with the current director of the Banting and Best Diabetes Centre, Dr. Gary Lewis, and Amira, they have collaborated and faithfully studied how insulin affects glucose uptake in muscle and fat, as well as hepatic glucose production in cells, rats, mice, dogs, and humans, over the past 4 decades. After beginning a postdoctoral fellowship with Dr. Luciano Rossetti, working on brain insulin action in New York City, I began meeting other scientists around the world, including Dr. Barbara Kahn, who, in parallel to Amira, has studied insulin action in fat and muscle at Harvard over the past 4 decades. In 2006 I returned to start my own lab at Toronto General Hospital Research Institute. It was there that I got to know Gary as well as other dedicated researchers such as Drs. Bernie Zinman, Dan Drucker, and Pat Brubaker, whose studies on insulin and GLP-1 action in cells, rodents, and humans along with many others around the world have helped to propel the field forward over the past 4–5 decades. To commemorate the 100th year anniversary of the discovery of insulin, I have worked alongside the editors of Cell Metabolism to bring together this Special Issue. In a Review, Bernie and Drs. Kramer and Retnakarn highlight how insulin and insulin analogs fare in lowering glucose levels in people with diabetes. Next, Amira together with Dr. Richter discuss how the insulin signaling pathway in the muscle is sufficient and necessary for exercise to regulate glucose uptake and metabolism, while Barbara and Dr. McGraw highlight the importance of adipocytes in mediating the ability of insulin to impact glucose metabolism. Gary, Adria, and Drs. Hahn and Carpentier then integrate and review how insulin directly regulates glucose production in the liver, as well as indirectly through action in the fat and the brain. We also present a Perspective from Drs. Nostro and Sneddon highlighting the literature from the past two decades on the potential of beta cell replacement therapy as well as generating insulin-producing cells from stem cells. In addition to Review and Perspective articles, this issue includes a timeline of the history of insulin and diabetes. We also share the personal stories from 18 scientists in the field as they reflect on the significance of the discovery of insulin and give their thoughts on what the future of insulin research might look like. In this issue we also highlight five original research articles, including the discovery of an insulin-sensitizing miRNA in exosomes released by macrophages, the possibility of using a prevalent bile acid from pigs as a diabetic therapy, and work showing how a reductive TCA cycle can drive glucose- and glutamine-stimulated insulin secretion. As one carefully goes through these reviews and research articles marking 4–5 decades of work by dedicated female and male scientists studying insulin action and secretion, the impact that the insulin discovery made 100 years ago has on humanity cannot be simply described in words. The success of insulin in treating diabetes is no question. But the impact of insulin discovery 100 years later via my personal experience, the legacy left behind by the Toronto team as recognized by the Banting and Best Diabetes Centre initiatives and funding programs, and all the current trainees who have contributed to these reviews and those around the world who are dedicating their lives in researching insulin and diabetes have undeniably cemented insulin discovery (in my opinion) as the GOAT of medical research. A final note: although my story is unique to me, my experience in Toronto (grounded by 100 years of history as witness) is not. I am very sure if you simply ask a former postdoc and/or graduate student from the Drucker lab in Toronto, they can more or less describe a comparable and enriched experience. As recognized in the review articles, Voices, and original research articles in this issue, we as diabetes, obesity, and metabolic researchers still have a lot to learn in the next 100 years. Perhaps history will repeat itself and we will have another GOAT in this field. Time will tell of the legacy that Tom Brady will leave behind 100 years later.