The Role of GIP in the Regulation of GLP-1 Satiety and Nausea

Abstract

Gastric inhibitory peptide (GIP) is best known for its role as an incretin hormone in control of blood glucose con-centrations. As a classic satiation signal, however, the literature illustrates a mixed picture of GIP involvement with an at best weak anorectic response profile being reported for GIP receptor (GIPR) signaling. Not surpris-ingly, the pursuit of exploiting the GIP system as a therapeutic target for diabetes and obesity has fallen behind that of the other gastrointestinal-derived incretin, glu-cagon-like peptide 1 (GLP-1). However, recent discover-ies highlighted here support potential therapeutic advantages of combinatorial therapies targeting GIP and GLP-1 systems together, with perhaps the most surprising finding that GIPR agonism may have antie-metic properties. As nausea and vomiting are the most common side effects of all existing GLP-1 pharmaco-therapies, the ability for GIP agonism to reduce GLP-1–induced illness behaviors but retain (if not enhance) weight loss and glycemic control may offer a new era in the treatment of obesity and diabetes.