ANTIDIABETIC ACTIONS OF CART
We have shown that CART is an important islet regulatory peptide and a constituent of human alpha- and beta cells. CART KO mice exhibit perturbed insulin secretion and glucose tolerance and CART augments glucose-stimulated insulin secretion (GSIS) and remarkably, CART further potentiates the insulinotropic effect of GLP-1. Furthermore, CART is a powerful inhibitor of glucagon secretion. Thus, CART is able to lower blood glucose both by enhancing insulin secretion and by reducing glucagon secretion. Furthermore, CART protects beta cells against glucotoxicity-induced cell death and CART is upregulated in islets of T2D patients and rodent models of T2D, as a response to hyperglycemia. Altogether these are properties that make CART-based agents highly interesting for treatment of T2D.
The yet unidentified CART receptor is a potential drug target for T2D therapy. Its identification would be an important step towards development of CART-based therapies. Our goal is to identify the CART-receptor and evaluate the potential for CART-based substances as a future treatment against T2D.