RESUMEN
The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by ß-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon ß-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.
Asunto(s)
Insulina/biosíntesis , Células Secretoras de Polipéptido Pancreático/metabolismo , Polipéptido Pancreático/metabolismo , Precursores de Proteínas/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal , Linaje de la Célula/genética , Femenino , Técnicas de Sustitución del Gen , Humanos , Células Secretoras de Insulina/clasificación , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/metabolismo , Masculino , Ratones , Ratones Transgénicos , Páncreas/citología , Páncreas/embriología , Páncreas/crecimiento & desarrollo , Polipéptido Pancreático/deficiencia , Polipéptido Pancreático/genética , Células Secretoras de Polipéptido Pancreático/clasificación , Células Secretoras de Polipéptido Pancreático/citología , Embarazo , RNA-SeqRESUMEN
BACKGROUND: TNF-related apoptosis inducing ligand (TRAIL) is a pleiotropic cytokine, which plays a key role in the immune system as well as in controlling the balance of apoptosis and proliferation in various organs and tissues. OBJECTIVE: To investigate the presence and levels of soluble TRAIL in human colostrum and milk. METHODS: The levels of soluble human TRAIL were measured in human colostrum (day 2 after delivery) and breast milk (day 5 after delivery). The presence of TRAIL was also measured in infant formula. RESULTS: Levels of soluble TRAIL in the colostrum and mature human milk were, respectively, at least 400 and 100 fold higher than those detected in human serum. No TRAIL was detected in formula. CONCLUSION: Human soluble TRAIL is present at extremely high levels in human colostrum and human milk and might have a significant role in mediating the anti-cancer activity of human milk.