Dataset Information
Deletion of histone deacetylase 3 in adult beta cells improves glucose tolerance via increased insulin secretion.
Ontology highlight
ABSTRACT: Objective
Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic ?-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in ?-cells of adult mice.Methods
An HDAC3 ?-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system. Induction of HDAC3 deletion was initiated at 8 weeks of age with administration of tamoxifen in corn oil (2 mg/day for 5 days). Mice were assayed for glucose tolerance, glucose-stimulated insulin secretion, and islet function 2 weeks after induction of the knockout. Transcriptional functions of HDAC3 were assessed by ChIP-seq as well as RNA-seq comparing control and ?-cell knockout islets.Results
HDAC3 ?-cell specific knockout (HDAC3?KO) did not increase total pancreatic insulin content or ?-cell mass. However, HDAC3?KO mice demonstrated markedly improved glucose tolerance. This improved glucose metabolism coincided with increased basal and glucose-stimulated insulin secretion in vivo as well as in isolated islets. Cistromic and transcriptomic analyses of pancreatic islets revealed that HDAC3 regulates multiple genes that contribute to glucose-stimulated insulin secretion.Conclusions
HDAC3 plays an important role in regulating insulin secretion in vivo, and therapeutic intervention may improve glucose homeostasis.
SUBMITTER: Remsberg JR
PROVIDER: S-EPMC5220396 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Publications
Deletion of histone deacetylase 3 in adult beta cells improves glucose tolerance via increased insulin secretion.
Molecular metabolism 20161122 1
<h4>Objective</h4>Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice.<h4>Methods</h4>An HDAC3 β ...[more]
