May 24, 2022

Diabetes, cardiovascular drug targets

Targeting receptors of the inflammatory lipid signaling molecule PGE2 may offer a new way to tackle both Type 2 diabetes and cardiovascular disease, Vanderbilt researchers have discovered.

by Leigh MacMillan

Type 2 diabetes, which affects more than 30 million Americans, increases risk of cardiovascular disease. Nearly 70% of people with Type 2 diabetes die from heart disease or stroke. 

Maureen Gannon, PhD, and colleagues investigated the role of the inflammatory lipid signaling molecule PGE2 — acting through EP3 and EP4 receptors — on heart muscle cell contractility and cardiac function in the setting of Type 2 diabetes. 

They found that inhibition of EP3 in db/db mice, an established model for Type 2 diabetes, improved cardiac function. In isolated cardiomyocytes, cultured in both normal and high glucose, EP3 blockade or EP4 activation enhanced contractility and calcium cycling. 

The findings, published in Physiological Reports, suggest that modulating EP3 and EP4 activity has beneficial effects on cardiomyocyte and overall heart function. Because EP3 and EP4 signaling also impact beta-cell proliferation, survival and function, the researchers propose that targeting these receptors may have positive effects on cardiovascular disease and Type 2 diabetes simultaneously.

Karin Bosma, PhD, and Spencer Andrei, PhD, at Vanderbilt and Monica Ghosh at Kent State University are co-first authors of the study. Derek Damron, PhD, at Kent State University is co-corresponding author with Gannon. The research was supported by grants from the National Institutes of Health (CA119925, DK007563, HL138519, DK120626), the U.S. Department of Defense and the U.S. Department of Veterans Affairs.