Nuclear receptor in the crosshairs of diabetes

Researchers at the Baylor College of Medicine and Scripps Florida have identified a new signaling pathway that could be targeted to treat type 2 diabetes.¹ The group has shown that activating the nuclear receptor LRH-1 pathway in mice can decrease fatty liver and increase insulin sensitivity without the typical weight gain caused by marketed PPAR agonists. The group's collaborators are running a pilot trial in prediabetic individuals to evaluate one LRH-1 agonist-dilauroyl phosphatidylcholine.

LRH-1 (nuclear receptor subfamily 5 group A member 2; NR5A2) is an orphan nuclear receptor best known for its role as a regulator of bile acid synthesis.² Because high levels of bile acids in the liver are known to reduce fatty liver³ and improve glucose homeostasis,⁴ the BCM and Scripps team began a search for compounds that activate LRH-1...