Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice.
Proc Natl Acad Sci U S A
; 107(11): 5208-13, 2010 Mar 16.
Article
em En
| MEDLINE
| ID: mdl-20194741
ABSTRACT
Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V(m)) and the cytosolic calcium level ([Ca(2+)](cyt)). We propose that TRPM5, a Ca(2+)-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca(2+)-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5(-/-) cells. Ca(2+)-imaging and electrophysiological analysis show that glucose-induced oscillations of V(m) and [Ca(2+)](cyt) have on average a reduced frequency in Trpm5(-/-) islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Sinalização do Cálcio
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Canais de Cátion TRPM
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Glucose
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article