Overexpression of PPARγ specifically in pancreatic β-cells exacerbates obesity-induced glucose intolerance, reduces β-cell mass, and alters islet lipid metabolism in male mice
| Autor: | Matej Orešič, Sarah L. Gray, Ali Asadi, Michael N. Craig, Christopher E. Uy, Robert K. Baker, K-Lynn N. Hogh, Alexander P. Rudecki, Jordie D. Fraser, Madeline Speck, Heli Nygren |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Ceramide Transgene Cell- och molekylärbiologi Peroxisome proliferator-activated receptor Cell Count Mice Transgenic Biology Carbohydrate metabolism Endocrinology and Diabetes chemistry.chemical_compound Islets of Langerhans Mice Endocrinology SDG 3 - Good Health and Well-being Internal medicine Insulin-Secreting Cells Genetic model Glucose Intolerance medicine Animals Obesity Receptor Cells Cultured chemistry.chemical_classification geography geography.geographical_feature_category Lipid metabolism Islet Lipid Metabolism Up-Regulation Mice Inbred C57BL PPAR gamma chemistry Organ Specificity Endokrinologi och diabetes Carbohydrate Metabolism Cell and Molecular Biology |
| Zdroj: | Hogh, K-L N, Craig, M N, Uy, C E, Nygren, H, Asadi, A, Speck, M, Fraser, J D, Rudecki, A P, Baker, R K, Orešič, M & Gray, S L 2014, ' Overexpression of PPARγ Specifically in Pancreatic β-Cells Exacerbates Obesity-Induced Glucose Intolerance, Reduces β-Cell Mass, and Alters Islet Lipid Metabolism in Male Mice ', Endocrinology, vol. 155, no. 10, pp. 3843-3852 . https://doi.org/10.1210/en.2014-1076 |
| DOI: | 10.1210/en.2014-1076 |
| Popis: | The contribution of peroxisomal proliferator-activated receptor (PPAR)-γ agonism in pancreatic β-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic β-cell PPARγ ablation have revealed a potential role for PPARγ in β-cell expansion in obesity but a limited role in normal β-cell physiology. Here we overexpressed PPARγ1 or PPARγ2 specifically in pancreatic β-cells of mice subjected to high-fat feeding using an associated adenovirus (β-PPARγ1-HFD and β-PPARγ2-HFD mice). We show β-cell-specific PPARγ1 or PPARγ2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased β-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice (β-eGFP-HFD mice). Analysis of islet lipid composition in β-PPARγ2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly β-PPARγ2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in β-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and β-oxidation. In summary, transgenic overexpression of PPARγ in β-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of β-oxidative genes, and reduced β-cell mass. Funding agencies:Canadian Diabetes Association University of Northern British Columbia Research Project Awards |
| Databáze: | OpenAIRE |
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