Improving insulin sensitivity
By Wendy Bindeman
Ambra Pozzi, professor of medicine and of molecular physiology and biophysics, first author Kakali Ghoshal (a postdoc in the Pozzi lab), and colleagues recently published a study showing that supplementation with an analog of a lipid metabolite called epoxyeicosatrienoic acid, which is involved in insulin signaling, reverses insulin resistance in the livers of mice lacking an EET-producing enzyme. Their findings were published last year in the journal Diabetes.
We sat down with Ghoshal to learn more about this exciting research.
What problem does your research address?
Diabetes is a significant and growing health concern in the United States and around the world. Diabetes is caused by impaired insulin sensitivity throughout the body, and the signaling mechanisms that help maintain insulin sensitivity are extremely complex.
Epoxyeicosatrienoic acids are part of a family of metabolites that contributes to insulin sensitivity. These metabolites have multiple signaling roles in cells and are known to help maintain insulin sensitivity, suggesting that they may be a target for the treatment of diabetes.
What were your findings?
We have shown that deletion of Cyp2c44, an enzyme that produces EETs in mice, causes insulin resistance in the liver. Administration of an EET analog or mimic restores insulin sensitivity in mice lacking the enzyme. We also explored the mechanism behind this effect and found that following insulin treatment, EETs prolong the retention of the insulin receptor on the cell surface of liver cells, which enhances signaling through the receptor and improves insulin sensitivity.
What do you hope will be achieved with the research results in the short and long terms?
The role of EETs in insulin resistance and diabetes is a novel area of investigation. We hope that studying this pathway will improve our understanding of diabetes biology and result in new treatment options to overcome insulin resistance.
Where is this research taking you next?
I will continue to study how EETs facilitate insulin sensitivity focusing on several pathways, including glucose and lipid metabolism. The ultimate goal is to better understand the mechanisms causing diabetes and to provide information that could result in improved patient care.
What are the benefits of this research?
Over 10% of Americans have been diagnosed with diabetes. Over time diabetes treatments stop working and new or additional treatments are required. Having more treatment options available for diabetic patients could improve their lifestyle. EET analogs may provide a new therapeutic approach for the treatment and management of insulin resistance.
This work was funded by the American Diabetes Association.
“EET analog treatment improves insulin signaling in a genetic mouse model of insulin resistance” was published in the journal Diabetes in October 2021.