Dataset Information

Rosiglitazone promotes PPAR?-dependent and -independent alterations in gene expression in mouse islets.

ABSTRACT: The glitazone class of insulin-sensitizing agents act, in part, by the activation of peroxisome proliferator-activated receptor (PPAR)-? in adipocytes. However, it is unclear whether the expression of PPAR? in the islets is essential for their potential ?-cell-sparing properties. To investigate the in vivo effects of rosiglitazone on ?-cell biology, we used an inducible, pancreatic and duodenal homeobox-1 enhancer element-driven, Cre recombinase to knockout PPAR? expression specifically in adult ?-cells (PPARgKO). Subjecting the PPARgKO mice to a chow diet led to virtually undetectable changes in glucose or insulin sensitivity, which was paralleled by minimal changes in islet gene expression. Similarly, challenging the mutant mice with a high-fat diet and treatment with rosiglitazone did not alter insulin sensitivity, glucose-stimulated insulin secretion, islet size, or proliferation in the knockout mice despite PPAR?-dependent and -independent changes in islet gene expression. These data suggest that PPAR? expression in the ?-cells is unlikely to be directly essential for normal ?-cell function or the insulin-sensitizing actions of rosiglitazone.

SUBMITTER: Welters HJ

PROVIDER: S-EPMC3512010 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rosiglitazone promotes PPARγ-dependent and -independent alterations in gene expression in mouse islets.

Welters Hannah J HJ El Ouaamari Abdelfattah A Kawamori Dan D Meyer John J Hu Jiang J Smith David M DM Kulkarni Rohit N RN

Endocrinology 20120717 10

The glitazone class of insulin-sensitizing agents act, in part, by the activation of peroxisome proliferator-activated receptor (PPAR)-γ in adipocytes. However, it is unclear whether the expression of PPARγ in the islets is essential for their potential β-cell-sparing properties. To investigate the in vivo effects of rosiglitazone on β-cell biology, we used an inducible, pancreatic and duodenal homeobox-1 enhancer element-driven, Cre recombinase to knockout PPARγ expression specifically in adult ...[more]

PMID: 22807489

Similar Datasets

Project description:BackgroundEnvironmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring exposed perinatally to multiple doses of BPA through the maternal diet.ResultsUsing a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 ?g BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response.ConclusionsIn this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways were identified and validated. The comprehensive methylome map presented here provides candidate loci underlying the role of early BPA exposure and later in life health and disease status.

Dataset Information

Rosiglitazone promotes PPAR?-dependent and -independent alterations in gene expression in mouse islets.

Publications

Rosiglitazone promotes PPARγ-dependent and -independent alterations in gene expression in mouse islets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets