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Overexpression of P...
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
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- Hogh, K-Lynn N. (författare)
- Northern Medical Program, University of Northern British Columbia, Prince George BC, Canada
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- Craig, Michael N. (författare)
- Northern Medical Program, University of Northern British Columbia, Prince George BC, Canada
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- Uy, Christopher E. (författare)
- Northern Medical Program, University of Northern British Columbia, Prince George BC, Canada
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- Nygren, Heli (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark
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- Asadi, Ali (författare)
- Department of Cellular and Physiological Sciences and Faculty of Medicine, University of British Columbia, Vancouver BC, Canada
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- Speck, Madeline (författare)
- Child and Family Research Institute, Vancouver BC, Canada
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Fraser, Jordie D. (författare)
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- Rudecki, Alexander P. (författare)
- Northern Medical Program, University of Northern British Columbia, Prince George BC, Canada
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- Baker, Robert K. (författare)
- Department of Cellular and Physiological Sciences and Faculty of Medicine, University of British Columbia, Vancouver BC, Canada
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark
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- Gray, Sarah L. (författare)
- Northern Medical Program, University of Northern British Columbia, Prince George BC, Canada
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(creator_code:org_t)
- Oxford University Press, 2014
- 2014
- Engelska.
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Ingår i: Endocrinology. - : Oxford University Press. - 0013-7227 .- 1945-7170. ; 155:10, s. 3843-3852
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Hogh, K-Lynn N.
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Craig, Michael N ...
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Uy, Christopher ...
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Nygren, Heli
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Asadi, Ali
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Speck, Madeline
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visa fler...
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Fraser, Jordie D ...
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Rudecki, Alexand ...
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Baker, Robert K.
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Oresic, Matej, 1 ...
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Gray, Sarah L.
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Endocrinology
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Örebro universitet