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An Overfeeding-Induced Obesity Mouse Model Reveals Necessity for Sin3a in Postnatal Peak ß-Cell Mass Acquisition.
Diabetes ; 71(11): 2395-2401, 2022 11 01.
Article en En | MEDLINE | ID: mdl-35944274
The increase of functional ß-cell mass is paramount to maintaining glucose homeostasis in the setting of systemic insulin resistance and/or augmented metabolic load. Understanding compensatory mechanisms that allow ß-cell mass adaptation may allow for the discovery of therapeutically actionable control nodes. In this study, we report the rapid and robust ß-cell hyperplasic effect in a mouse model of overfeeding-induced obesity (OIO) based on direct gastric caloric infusion. By performing RNA sequencing in islets isolated from OIO mice, we identified Sin3a as a novel transcriptional regulator of ß-cell mass adaptation. ß-Cell-specific Sin3a knockout animals showed profound diabetes due to defective acquisition of postnatal ß-cell mass. These findings reveal a novel regulatory pathway in ß-cell proliferation and validate OIO as a model for discovery of other mechanistic determinants of ß-cell adaptation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Células Secretoras de Insulina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Células Secretoras de Insulina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos