Incretin Receptors in the Peripheral Nervous System: Implications for Obesity Treatment and Peripheral Neuropathy

There is currently a revolution in the pharmacological treatment of obesity and diabetes with newly available agonists of incretin receptors. The health benefits of these novel treatments include not only metabolic effects, but also improvements in brain neurodegenerative conditions. Receptors for incretins were described in the hypothalamic appetite regulatory center, however, their expression in the peripheral nervous system (PNS) has been largely overlooked, despite likely contributing important effects. For example, the PNS is essential for the control of numerous metabolically-relevant pathways in tissues like liver, adipose, intestine, muscle, and more, and incretin receptors are found on nerves innervating some, if not all, of these metabolically-important tissues. In this article we summarize the knowledge to date regarding incretin receptors and incretin drug actions in the PNS, as well as PNS control over incretin release, and the related implications for metabolic disease states that are accompanied by peripheral neuropathy.