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Rosiglitazone Promotes PPARγ-Dependent and -Independent Alterations in Gene Expression in Mouse Islets
- Source :
- Endocrinology. 153:4593-4599
- Publication Year :
- 2012
- Publisher :
- The Endocrine Society, 2012.
-
Abstract
- 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 β-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 PPARγ-dependent and -independent changes in islet gene expression. These data suggest that PPARγ expression in the β-cells is unlikely to be directly essential for normal β-cell function or the insulin-sensitizing actions of rosiglitazone.
- Subjects :
- Blood Glucose
medicine.medical_specialty
medicine.medical_treatment
Peroxisome proliferator-activated receptor
Cre recombinase
Mice, Transgenic
Biology
Diet, High-Fat
Rosiglitazone
Islets of Langerhans
Mice
Endocrinology
Internal medicine
Gene expression
medicine
Animals
Hypoglycemic Agents
Insulin
Regulation of gene expression
chemistry.chemical_classification
geography
geography.geographical_feature_category
C-Peptide
Islet
PPAR gamma
Gene Expression Regulation
chemistry
Knockout mouse
Thiazolidinediones
Brief Reports
medicine.drug
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 153
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....3dc45020c638697b22e0924b41b05dc1