Gerald I. Shulman, MD, PhD, George R. Cowgill Professor of Medicine (Endocrinology) and professor of cellular and molecular physiology, and co-director of the Yale Diabetes Research Center, received the 2023 European Association for the Study of Diabetes (EASD)-Lilly Centennial Anniversary Prize. The award recognizes individual researchers who have made landmark achievements in the pathogenesis of diabetes.
“It’s a wonderful acknowledgement of the contributions in this area by my students, postdoctoral fellows, and collaborators, who are all working to understand the causes of insulin resistance and type 2 diabetes to improve the lives of our patients and prevent cardiometabolic disease,” Shulman said.
As part of his award, Shulman will give a lecture titled “The Role of Ectopic Lipid in Insulin Resistance and Cardiometabolic Disease” at the EASD annual meeting, in Hamburg, Germany, on October 6, 2023.
Over the past three decades, Shulman has been studying the molecular basis for insulin resistance. Insulin resistance is the major factor responsible for the development of type 2 diabetes, which is a leading cause of kidney failure, nontraumatic loss of limb, and blindness in working-age adults. It is also a major factor in the development of cardiovascular disease, fatty liver disease, and Alzheimer’s, according to Shulman, and has likely played a role in the marked increase over the past few decades in the incidence of obesity-associated cancers, such as breast, pancreatic, colon, and liver cancer.
Through his research, Shulman has found that insulin resistance in individuals with obesity, type 2 diabetes, as well as in young lean offspring of parents with type 2 diabetes, can be attributed to a defect in insulin-stimulated muscle glycogen synthesis, which in turn can be attributed to a defect in insulin-stimulated glucose transport activity. His group went on to show that this defect in insulin-stimulated glucose transport activity in muscle could be attributed to increased ectopic lipid in skeletal muscle. The researchers found that when muscle becomes insulin resistant, it can no longer store the ingested glucose as muscle glycogen, and the ingested glucose is diverted to the liver, where it is converted to fat, leading to fatty liver disease, metabolic-associated steatohepatitis (MASH), and hyperlipidemia.
“This mechanism by which ectopic lipid in liver and muscle promotes insulin resistance explains why even lean individuals can be susceptible to insulin resistance and cardiometamolic disease and how weight loss and agents that promote weight loss, such as the new class of GLP-1 agonists, reverse insulin resistance and type 2 diabetes,” Shulman said.
Shulman’s work has led to several paradigm shifts in the understanding of type 2 diabetes, as well as the development of new therapeutics that reduce excess ectopic lipid in the liver and muscle by promoting increase fat oxidation in these organs.
“Given our new understanding of the molecular basis of insulin resistance and the new drugs in development to target this mechanism, I’m very optimistic about the future of treating insulin resistance and cardiometabolic disease to promote metabolic health,” Shulman said.
Yale’s Section of Endocrinology & Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more about their work, visit Endocrinology & Metabolism.