PTEN deletion in pancreatic α-cells protects against high-fat diet-induced hyperglucagonemia and insulin resistance.
Diabetes
; 64(1): 147-57, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25092678
ABSTRACT
An aberrant increase in circulating catabolic hormone glucagon contributes to type 2 diabetes pathogenesis. However, mechanisms regulating glucagon secretion and α-cell mass are not well understood. In this study, we aimed to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling is an important regulator of α-cell function. Mice with deletion of PTEN, a negative regulator of this pathway, in α-cells show reduced circulating glucagon levels and attenuated l-arginine-stimulated glucagon secretion both in vivo and in vitro. This hypoglucagonemic state is maintained after high-fat-diet feeding, leading to reduced expression of hepatic glycogenolytic and gluconeogenic genes. These beneficial effects protected high-fat diet-fed mice against hyperglycemia and insulin resistance. The data demonstrate an inhibitory role of PI3K signaling on α-cell function and provide experimental evidence for enhancing α-cell PI3K signaling for diabetes treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Glucagon
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Diabetes Mellitus Tipo 2
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Células Secretoras de Glucagon
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PTEN Fosfo-Hidrolase
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article