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| Status |
Public on Apr 20, 2017 |
| Title |
Glucose sensing by skeletal myocytes couples nutrient signaling to systemic homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in this tissue contributes to hyperglycemia in type 1 and type 2 diabetes. While glucose is known to stimulate insulin secretion by pancreatic b cells, whether it directly engages nutrient-sensing pathways in skeletal muscle to regulate glucose metabolism remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improves postprandial glucose disposal in mice, whereas the muscle-specific ablation impaired insulin action and led to glucose intolerance. Mechanistically, glucose triggers a rapid calcium response in myocytes that acts on the class IIa histone deacetylase HDAC5, leading to Baf60c induction and insulin-independent AKT activation. The pathway is engaged by the anti-diabetic drugs sulfonylureas, suggesting that its therapeutic activation may have beneficial effects on glycemic control in diabetes.
We used microarrays to elucidate the role of of Baf60c in transcriptional regulation by glucose in skeletal myocytes.
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| Overall design |
C2C12 myoblasts were transduced with retroviruses expressing shRNAs targeting control or mouse Baf60c, differentiated into myotubes, and treated with 1 mM or 10 mM glucose for 12 h. Then cells were harvested for RNA isolation and microarray hybridization using Affymetrix Mouse Gene ST 2.1 Arrays. Two independent biological replicates for each treatment were included in this study.
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| Contributor(s) |
Meng Z, Gong J, Chen Z, Sun J, Xiao Y, Li Y, Liu J, Xu S, Lin JD |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 05, 2016 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Zhuoxian Meng |
| E-mail(s) |
zxmeng@umich.edu
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| Phone |
7346153510
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| Organization name |
University of Michigan
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| Street address |
210 Washtenaw Ave
|
| City |
Ann Arbor |
| State/province |
Michigan |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA317425 |
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