We investigate mechanisms in mouse and cell culture models and translate these findings through our collaborations with clinicians. Our goal is to apply our findings to improve the prevention and treatment of age-related metabolic disease.
Glucagon Signaling in Aging and Healthspan
Obesity and type 2 diabetes accelerate aging, shortening the duration of healthspan. Conversely, chronic calorie restriction extends healthspan. Most research aimed at understanding the mechanism by which obesity accelerates aging and calorie restriction slows aging has focused on insulin and downstream signaling cascades. Glucagon, a hormone that counter-regulates insulin, is commonly affected by these same interventions. Thus, it is essential to understand the role of glucagon in aging.
Our research examines the role of glucagon signaling in:
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Obesity-accelerated aging
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Healthspan extension promoted by calorie restriction
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Exercise-mediated improvements in metabolic and physical function
Insulin resistance and elevated insulin are key to the metabolic disturbances in type II diabetes mellitus. Yet, elevated glucagon, common to diabetes, is equally important in the metabolic abnormalities in diabetes. We have shown that nutritional state differentially affects glucagon secretion in obesity. In turn, the glucagon:insulin ratio is dysregulated in obesity. Our work aims to understand the metabolic consequences of a dysregulated glucagon response to both fasting and re-feeding.
Learn more and view Dr. Stern's webinar hosted by Mercodia:
Glucagon Signaling in Obesity and Type 2 Diabetes
Obesity-Driven Liver Cancer
Obesity is the leading cause of multiple solid cancers. In fact, the risk of developing hepatocellular carcinoma (HCC) is more than doubled in obese people with Type 2 diabetes. To identify new drug targets to treat HCC, we apply a chemical model of accelerated hepatocellular carcinoma to examine the effects of hepatic lipid accumulation and dysregulated hormone signaling on hepatocellular carcinoma development and progression.