Welcome to the Capozzi Laboratory

We are seeking to understand how hormones control nutrient metabolism in health and metabolic disease.

Research:

Metabolic diseases such as diabetes and steatotic liver disease are characterized by changes in nutrient use and storage, due in large part to altered secretion or action of key hormones, insulin and glucagon, from the pancreatic islet. Insulin is a prandial hormone, with its secretion stimulated by ingestion of carbohydrates to facilitate glucose utilization or storage after a meal. Conversely, glucagon is predominantly considered a fasting hormone where it elevates circulating glucose through stimulation of hepatic glucose output in times of nutrient deficit. However, glucagon and insulin are both secreted in response to normal mixed nutrient feeding, and the impact of their co-stimulation on glucose metabolism remains incompletely defined. Recent evidence has pointed to unique signaling mechanisms and actions of insulin and glucagon cross-talk in the liver, the primary organ that possesses both insulin and glucagon receptors. The liver is a hub for nutrient metabolism, integrating carbohydrate, protein and fat synthesis, storage and utilization to supply energy to the body depending on the nutritional environment.

We hypothesize that improving nutrient deposition in the liver may allow for greater systemic control of glucose and fat storage during disease. Thus, the first goal of our research program is to understand how glucagon and insulin interact to regulate glucose metabolism in response to a meal. We then want to use that knowledge to understand how metabolic disease alters glucose storage in disease.

The incretin class of drugs has received a lot of attention for their strong effects on glucose lowering in people with diabetes and body weight reduction in people with diabetes and/or obesity. The incretin hormone, GLP-1, reduces glucagon while stimulating insulin, while GIP increases both hormones. Combining GLP-1 action with GIP has a better effect on metabolic outcomes than GLP-1 receptor mono-agonism. We plan to determine how different combinations of incretin treatments regulate hepatic glucose use and storage through their actions on pancreatic hormones.