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An Overfeeding-Induced Obesity Mouse Model Reveals Necessity for Sin3a in Postnatal Peak β-Cell Mass Acquisition.

Authors :
Bartolomé A
Ravussin Y
Yu J
Ferrante AW
Pajvani UB
Source :
Diabetes [Diabetes] 2022 Nov 01; Vol. 71 (11), pp. 2395-2401.
Publication Year :
2022

Abstract

The increase of functional β-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 β-cell mass adaptation may allow for the discovery of therapeutically actionable control nodes. In this study, we report the rapid and robust β-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 β-cell mass adaptation. β-Cell-specific Sin3a knockout animals showed profound diabetes due to defective acquisition of postnatal β-cell mass. These findings reveal a novel regulatory pathway in β-cell proliferation and validate OIO as a model for discovery of other mechanistic determinants of β-cell adaptation.<br /> (© 2022 by the American Diabetes Association.)

Details

Language :
English
ISSN :
1939-327X
Volume :
71
Issue :
11
Database :
MEDLINE
Journal :
Diabetes
Publication Type :
Academic Journal
Accession number :
35944274
Full Text :
https://doi.org/10.2337/db22-0306