Lab Website: https://imai.lab.uiowa.edu

A role of lipid droplet protein in insulin secretion and islet health

Dr. Imai’s research aims to understand the mechanism behind pancreatic beta cell failure in type 2 diabetes. Although type 2 diabetes is triggered by insulin resistance due to overnutrition, the reduction of functional beta cell mass is ultimately responsible for inability to maintain glucose homeostasis in type 2 diabetes. Thus, the restoration of functional beta cell mass is an important goal of diabetes therapy and yet has not been achieved in therapeutics available now.

Interestingly, fatty acids acutely augment insulin secretio However, prolonged exposure to fatty acids such as seen in overnutrition impairs beta cell health. Her laboratory focuses on how lipid droplet proteins optimize intracellular lipid metabolism to support insulin secretion while protecting beta cells from excessive lipid load. Her research uses human islet cells, mouse islets, and beta cell lines in which lipid droplet proteins and lipid metabolism enzymes are genetically modified as the models to address the regulation of lipid metabolism and its impact on islet function.

An additional area of her research includes protein s-palmitoylation, a modification of cystine by fatty acids as a down-stream target of lipid droplet proteins. While it is known that protein s-palmitoylation is highly prevalent with functional consequence, there currently is limited information regarding this class of modification in beta cells. We have systematically screened DHHC enzymes that catalyze protein s-palmitoylation and identified enzymes with a role in insulin secretion. We are actively dissecting the mechanism by which DHHC supports insulin secretion.

Ultimately, her research team seeks to combine knowledge from key projects to identify a new target to improve beta cell health and function as a treatment for diabetes.



PubMed link

Department/Program Affiliations:
Internal Medicine