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| Status |
Public on Jun 30, 2016 |
| Title |
Adipose Rab10 Knockout Causes Insulin Resistance through Impaired Glucose Uptake |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Insulin action in adipocytes affects whole-body insulin sensitivity. Studies of adipose-specific Glut4 knockout mice have established that adipose Glut4 contributes to the control of systemic glucose homeostasis. Presumably, this reflects a role for Glut4-mediated glucose transport in the regulation of secreted adipokines. In cultured 3T3-L1 adipocytes, Rab10 GTPase is required for insulin-stimulated translocation of Glut4 (Sano et al., 2007). The physiological importance of adipose Rab10 and the significance of its role in the control of Glut4 vesicle trafficking in vivo are unknown. Here we report that adipocytes from adipose-specific Rab10 knockout mice have a ~50% reduction in glucose uptake and Glut4 translocation to the cell surface in response to insulin, demonstrating a role for Rab10 in Glut4 trafficking. Moreover, hyperinsulinemic-euglycemic clamp shows decreased whole-body glucose uptake as well as impaired suppression of hepatic glucose production in adipose Rab10 knockout mice. Thus, fully functional Glut4 vesicle trafficking in adipocytes is critical for maintaining insulin sensitivity. Comparative transcriptome analysis of perigonadal adipose tissue demonstrates significant transcriptional similarities between adipose Rab10 knockout mice and adipose Glut4 knockout mice, consistent with the notion that the phenotypic similarities between the two models are mediated by reduced insulin-stimulated glucose transport into adipocytes.
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| |
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| Overall design |
Transcriptome sequencing of perigonadal white adipose tissue
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| |
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| Contributor(s) |
Vazirani R, McGraw TE, Elemento O, Verma A |
| Citation(s) |
27207531 |
| Submission date |
Jun 22, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Akanksha Verma |
| Organization name |
Weill Cornell Medical College
|
| Department |
Department of Physiology and Biophysics
|
| Street address |
1300, York Avenue
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA287703 |
| SRA |
SRP059753 |
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