TRPM7 is a crucial regulator of pancreatic endocrine development and high-fat-diet-induced ß-cell proliferation.
Development
; 148(16)2021 08 15.
Article
en En
| MEDLINE
| ID: mdl-34345920
ABSTRACT
The melastatin subfamily of the transient receptor potential channels (TRPM) are regulators of pancreatic ß-cell function. TRPM7 is the most abundant islet TRPM channel; however, the role of TRPM7 in ß-cell function has not been determined. Here, we used various spatiotemporal transgenic mouse models to investigate how TRPM7 knockout influences pancreatic endocrine development, proliferation and function. Ablation of TRPM7 within pancreatic progenitors reduced pancreatic size, and α-cell and ß-cell mass. This resulted in modestly impaired glucose tolerance. However, TRPM7 ablation following endocrine specification or in adult mice did not impact endocrine expansion or glucose tolerance. As TRPM7 regulates cell proliferation, we assessed how TRPM7 influences ß-cell hyperplasia under insulin-resistant conditions. ß-Cell proliferation induced by high-fat diet was significantly decreased in TRPM7-deficient ß-cells. The endocrine roles of TRPM7 may be influenced by cation flux through the channel, and indeed we found that TRPM7 ablation altered ß-cell Mg2+ and reduced the magnitude of elevation in ß-cell Mg2+ during proliferation. Together, these findings revealed that TRPM7 controls pancreatic development and ß-cell proliferation, which is likely due to regulation of Mg2+ homeostasis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Páncreas
/
Proliferación Celular
/
Células Secretoras de Insulina
/
Canales Catiónicos TRPM
/
Dieta Alta en Grasa
/
Secreción de Insulina
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos