Pancreatic ß-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human Diabetes.
Diabetes
; 66(2): 426-436, 2017 02.
Article
en En
| MEDLINE
| ID: mdl-27864307
ABSTRACT
ß-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of ß-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated ß-cells after exposure to severe hyperglycemia. Gastrin expression in adult ß-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of ß-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human ß-cell reprogramming in diabetes.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Gastrinas
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Tipo de estudio:
Observational_studies
Límite:
Aged
/
Aged80
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Diabetes
Año:
2017
Tipo del documento:
Article
País de afiliación:
Israel