The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone released from the epithelium of the upper small intestine. While GIP shares common actions on the pancreatic beta cell with glucagon-like peptide-1 (GLP-1), unlike GLP-1, GIP presents a complex target for the development of diabetes and obesity therapies due to its extra-pancreatic effects on fat mass. Recent pharmacological developments, however, have provided insight into a previously unrecognized role for GIP receptor (GIPR) signaling in regulating appetite. Additionally, GIP-based therapeutics have demonstrated promising neuroprotective properties. Together these observations identify an important central component of the GIP/GIPR signaling axis, and have triggered a resurgence of research interest into the central actions of GIP. In this review, we discuss what is currently known about where GIP may act in the central nervous system (CNS), the characteristics of its target cell populations, and the physiological effects of manipulating the activity Gipr-expressing cells in the brain.