Blocking Ca2+ Channel ß3 Subunit Reverses Diabetes.
Cell Rep
; 24(4): 922-934, 2018 07 24.
Article
en En
| MEDLINE
| ID: mdl-30044988
ABSTRACT
Voltage-gated Ca2+ channels (Cav) are essential for pancreatic beta cell function as they mediate Ca2+ influx, which leads to insulin exocytosis. The ß3 subunit of Cav (Cavß3) has been suggested to regulate cytosolic Ca2+ ([Ca2+]i) oscillation frequency and insulin secretion under physiological conditions, but its role in diabetes is unclear. Here, we report that islets from diabetic mice show Cavß3 overexpression, altered [Ca2+]i dynamics, and impaired insulin secretion upon glucose stimulation. Consequently, in high-fat diet (HFD)-induced diabetes, Cavß3-deficient (Cavß3-/-) mice showed improved islet function and enhanced glucose tolerance. Normalization of Cavß3 expression in ob/ob islets by an antisense oligonucleotide rescued the altered [Ca2+]i dynamics and impaired insulin secretion. Importantly, transplantation of Cavß3-/- islets into the anterior chamber of the eye improved glucose tolerance in HFD-fed mice. Cavß3 overexpression in human islets also impaired insulin secretion. We thus suggest that Cavß3 may serve as a druggable target for diabetes treatment.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Canales de Calcio
/
Oligonucleótidos Antisentido
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Islotes Pancreáticos
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Canales de Potasio con Entrada de Voltaje
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Diabetes Mellitus Experimental
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Año:
2018
Tipo del documento:
Article