Mitochondrial signals drive insulin secretion in the pancreatic ß-cell.
Mol Cell Endocrinol
; 353(1-2): 128-37, 2012 Apr 28.
Article
en En
| MEDLINE
| ID: mdl-21784130
ABSTRACT
ß-Cell nutrient sensing depends on mitochondrial function. Oxidation of nutrient-derived metabolites in the mitochondria leads to plasma membrane depolarization, Ca(2+) influx and insulin granule exocytosis. Subsequent mitochondrial Ca(2+) uptake further accelerates metabolism and oxidative phosphorylation. Nutrient activation also increases the mitochondrial matrix pH. This alkalinization is required to maintain elevated insulin secretion during prolonged nutrient stimulation. Together the mitochondrial Ca(2+) rise and matrix alkalinization assure optimal ATP synthesis necessary for efficient activation of the triggering pathway of insulin secretion. The sustained, amplifying pathway of insulin release also depends on mitochondrial Ca(2+) signals, which likely influence the generation of glucose-derived metabolites serving as coupling factors. Therefore, mitochondria are both recipients and generators of signals essential for metabolism-secretion coupling. Activation of these signaling pathways would be an attractive target for the improvement of ß-cell function and the treatment of type 2 diabetes.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Insulina
/
Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Suiza