The "cryptic" mechanism of action of glucagon-like peptide-2.
Am J Physiol Gastrointest Liver Physiol
; 301(1): G1-8, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21527727
ABSTRACT
Glucagon-like peptide-2 (GLP-2) is a peptide hormone with multiple beneficial effects on the intestine, including expansion of the mucosal surface area through stimulation of crypt cell proliferation, as well as enhancement of nutrient digestion and absorption. Recent advances in clinical trials involving GLP-2 necessitate elucidation of the exact signaling pathways by which GLP-2 acts. In particular, the GLP-2 receptor has been localized to several intestinal cell types that do not include the proliferating crypt cells, and the actions of GLP-2 have thus been linked to a complex network of indirect mediators that induce diverse signaling pathways. The intestinotropic actions of GLP-2 on the colon have been shown to be mediated through the actions of keratinocyte growth factor and insulin-like growth factor (IGF)-2, whereas small intestinal growth has been linked to IGF-1, IGF-2, and ErbB ligands, as well as the IGF-1 receptor and ErbB. The cellular source of these mediators remains unclear, but it likely includes the intestinal subepithelial myofibroblasts. Conversely, the anti-inflammatory and blood flow effects of GLP-2 are dependent on vasoactive intestinal polypeptide released from submucosal enteric neurons and nitric oxide, respectively. Finally, recent studies have suggested that GLP-2 not only modulates intestinal stem cell behavior but may also promote carcinogenesis in models of sporadic colon cancer. Further consideration of the molecular cross-talk and downstream signaling pathways mediating the intestinotropic effects of GLP-2 is clearly warranted.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transformación Celular Neoplásica
/
Antiinflamatorios no Esteroideos
/
Péptido 2 Similar al Glucagón
/
Intestinos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Physiol Gastrointest Liver Physiol
Asunto de la revista:
FISIOLOGIA
/
GASTROENTEROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Canadá