Guanylin peptides (GPs) and their receptor, guanylate cyclase C (GC-C), have recently become a topic of great interest in metabolic research. Guanylin and uroguanylin are the most investigated GPs and they belong to a larger family of natriuretic peptides. GPs play a physiological role in regulation of electrolyte balance via the intestine and the kidney by regulating the energy balance via their action in the brain. In addition to well-known cGMP signaling pathway, GPs activate a GC-C independent signaling pathway in the intestine, kidneys, as well as the brain. Even though the existence of two separate signaling pathways for other natriuretic peptides is well investigated, the GC-C independent signaling pathway is still a mystery. In this review, we summarize the recent discoveries related to the actions of GPs with special attention to the GC-C independent signaling pathway. We also discuss the main controversies in the field. Sex differences in GPs action via GC-C dependent and independent signaling pathway could address some of the discrepancies in literature. Here, we overview the role of GPs and their signaling pathways in the most common diseases of the modern world.
Ca2+ signaling pathway, cGMP, Natriuretic peptides, Sex differences, Energy balance, Tripartite synapse, Hypothalamus, Midbrain