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Quantitative analysis of orphan nuclear receptors in insulin-resistant C2C12 skeletal muscle cells
Citation
Chew, GS and Gawned, M and Molina, E and Myers, SA, Quantitative analysis of orphan nuclear receptors in insulin-resistant C2C12 skeletal muscle cells, Journal of Diabetes & Metabolism, 6, (11) Article 626. ISSN 2155-6156 (2015) [Refereed Article]
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Copyright Statement
© 2015 Chew GS, et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/
DOI: doi:10.4172/2155-6156.1000626
Abstract
Orphan nuclear receptors (ONR) are members of the nuclear receptor (NR) super family of transcription factors that have been known to play a major role in lipid and glucose metabolism in skeletal muscle. Recently, pharmacological evidence supports the view that stimulation of NR alleviates Type 2 Diabetes (T2D). However the ligands and physiological functions of ONRs still remain unknown. To date, no systematic studies have been carried out to screen for ONRs expressed in insulin resistant skeletal muscle cells. Therefore, in this study, we have established a model for insulin resistance (IR) by treating C2C12 skeletal muscle cells with insulin (10nM) for 48 hours. Western Blot analysis of phosphorylated AKT confirmed IR. By quantitative PCR, we identified that a number of the ONRs respond significantly during the progression of cellular insulin resistance which included Couptf1, Coup-tf2, Pparβ, NR4As, Reverbα, and Rorα, some of which have been associated with fatty acid oxidation regulation and glucose homeostasis and therefore could play a role in the aetiology of this disorder. Highlighted were observed increased mRNA expression levels of other ONRs in insulin resistant C2C12 skeletal muscle cells, indicated that these ONRs could potentially play a pivotal regulatory role of insulin secretion in lipid metabolism. Taken together, this study has successfully contributed to the analysis of ONR in IR, and has filled in an important void in the study of these receptors as potential targets in the pharmacological treatment of this disorder.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | orphan nuclear receptors, transcription factors, type 2 diabetes, insulin resistance |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and cell biology |
| Research Field: | Cell metabolism |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Myers, SA (Dr Stephen Myers) |
| ID Code: | 105077 |
| Year Published: | 2015 |
| Deposited By: | Health Sciences |
| Deposited On: | 2015-12-07 |
| Last Modified: | 2016-06-14 |
| Downloads: | 136 View Download Statistics |
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