A Novel Type 2 Diabetes Treatment Biased Agonists for Free Fatty Acid Receptor 2

Type 2 diabetes (T2D) is a disease reaching epidemic levels in our society. Because there is insufficient treatment approaches for T2D, novel therapies are needed. One of the major defects in T2D is insufficient glucose stimulated insulin secretion (GSIS), in particular, when insulin resistance develops. Therefore, we previously sought to identify novel genes that could be potentially targeted to augment GSIS. Through a variety of studies, we identified our target gene of interest, FFAR2, based initially on the observation that the expression of this gene was altered in islets by insulin resistance. These data suggested FFAR2 might be important in insulin secretion. Further exploring, we examined its biological role using a mouse model where FFAR2 is genetically deleted. In this model, evidence suggests that FFAR2 has an important role in GSIS. Considering that this gene is Gprotein coupled receptor (GPCR), which is a class of receptors that are highly ‘druggable’, we propose to develop agonists for FFAR2 that selectively regulate aspects of FFAR2 function that will be important in augmenting GSIS, and therefore result in a novel T2D treatment approach.