Prostaglandin EP3 receptor signaling is required to prevent insulin hypersecretion and metabolic dysfunction in a non-obese mouse model of insulin resistance

Abstract

Islet prostaglandin EP3 receptor (EP3) signaling is well known as upregulated in the pathophysiological conditions of type 2 diabetes, contributing to β-cell dysfunction. Unexpected findings in mouse models of non-obese insulin sensitivity and resistance provide a new dimension to our understanding of EP3 as a key modulator of insulin secretion. A previously unknown relationship between mouse insulin resistance and the penetrance of rat insulin promoter-driven germline floxed allele recombination is critical to consider when creating β-cell-specific knockouts.