title: Wnt and incretin connections.
abstract: WNT signaling is emerging as a global regulator of metabolism, targeting multiple tissues. This is achieved either directly through Wnt receptors, or indirectly through the action of incretins, hormones that enhance glucose-stimulated insulin secretion and target extrapancreatic organs that cooperatively control whole body energy balance. WNT increases expression of incretins through evolutionarily conserved elements located within their proximal promoters. Wnt-responsive elements at the Incretin promoters may exhibit a high degree of selectivity for specific WNT effectors. Additionally, Incretins may modulate Wnt signaling and vice versa. Wnt-dependent modulation of incretin action in β-pancreatic cells is suspected because the expression levels of Incretin receptors correlate with those of the Wnt effector TCF7L2. Conversely, Wnt signaling is enhanced by Incretin binding to their receptors which induces cAMP accumulation followed by stabilization of the Wnt effector: β-catenin. High glucose and/or lipids control the number of Incretin receptors exhibited by β cells. Whether these nutrients and/or the Incretins control Wnt receptors (either their expression or signaling) remains to be further elucidated. Thus, Wnt controls the expression of incretins and modulate their signaling at pancreatic cells. Signaling by Wnt and incretins appears to be interconnected at multiple levels. The in vivo significance of incretin induction by Wnt is unknown as it is the nature and origin of Wnt signals in enteroendocrine cells but opens an intense research that promises many surprises; in vitro approaches may be used for mechanistic studies and animal models for physiological perspectives.
authors.affiliation: Facultad de Ciencias de la Salud (Health Science Faculty), Universidad Rey Juan Carlos, Alcorcon, Madrid, Spain.
authors.forename: Custodia
authors.initials: C
authors.lastname: García-Jiménez
mesh_terms: D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051379:Mice; D051153:Wnt Proteins / Q000502:physiology*
chemical_list: D051153:Wnt Proteins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1