ß-Cell preservation and regeneration in diabetes by modulation of ß-cell Ca²âº homeostasis.
Diabetes Obes Metab
; 14 Suppl 3: 136-42, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22928574
Ca(2+) extrusion from the ß-cell is mediated by two processes the Na/Ca exchanger (NCX) and the plasma membrane Ca(2+) -ATPase (PMCA). Gain of function studies show that overexpression of NCX or PMCA leads to endoplasmic reticulum (ER) Ca(2+) depletion with subsequent ER stress, decrease in ß-cell proliferation and ß-cell death by apoptosis. Interestingly, chronic exposure to cytokines or high free fatty acid concentrations also induce ER Ca(2+) depletion and ß-cell death in diabetes. Loss of function studies show, on the contrary, that heterozygous inactivation of NCX1 (Ncx1(+/-)) leads to an increase in ß-cell function (insulin production and release), and a fivefold increase in both ß-cell mass and proliferation. The mutation also increases ß-cell resistance to hypoxia, and Ncx1(+/-) islets show a two to four times higher rate of diabetes cure than Ncx1(+/+) islets when transplanted in diabetic animals. Thus, down-regulation of the Na/Ca exchanger leads to various changes in ß-cell function that are opposite to the major abnormalities seen in diabetes. This provides a unique model for the prevention and treatment of ß-cell dysfunction in diabetes and following islet transplantation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regeneración
/
Calcio
/
Intercambiador de Sodio-Calcio
/
Diabetes Mellitus Tipo 1
/
Diabetes Mellitus Tipo 2
/
Retículo Endoplásmico
/
Células Secretoras de Insulina
/
Estrés del Retículo Endoplásmico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2012
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Reino Unido