|
| Status |
Public on Aug 10, 2023 |
| Title |
Ribosome profiling of metformin treatment in primary murine hepatocytes in WT, Raptor Ser-Ala mutant, Tsc2-null, Raptor mutant;Tsc2-null, and Ampk-null cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Despite being the frontline therapy for Type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill-defined. Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB. But several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1. Here we investigated the role of direct AMPK-mediated serine phosphorylation of RAPTOR in a new RaptorAA mouse model, in which AMPK phospho-serine sites Ser722 and Ser792 of RAPTOR were mutated to alanine. Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for the translational response to metformin.
|
| |
|
| Overall design |
2h treatment of 2mM Metformin or 0.1uM INK-128 in serum-starved primary murine hepatocytes in the absence or presence of 15 minute pre-treatment with 1nM Insulin
|
| |
|
| Contributor(s) |
Van Nostrand JL, Shaw RJ, Hellberg K, Luo E, Van Nostrand EL, Dayn A, Yu J, Shokhirev MN, Dayn Y, Yeo GW |
| Citation(s) |
32912901 |
| |
| Submission date |
Aug 28, 2020 |
| Last update date |
Aug 10, 2023 |
| Contact name |
April Elizabeth Williams |
| E-mail(s) |
apriljack06@gmail.com, awilliams@salk.edu
|
| Phone |
7345461645
|
| Organization name |
Salk Institute for Biological Studies
|
| Department |
IGC
|
| Street address |
10010 N Torrey Pines Rd
|
| City |
San Diego |
| State/province |
California |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (66)
|
|
| This SubSeries is part of SuperSeries: |
| GSE157051 |
AMPK regulation of Raptor and TSC2 mediate Metformin effects on transcriptional control of anabolism and inflammation |
|
| Relations |
| BioProject |
PRJNA659995 |
| SRA |
SRP279200 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157050_AATSC_ins_PvsI.edgeR.txt.gz |
261.2 Kb |
(ftp)(http) |
TXT |
| GSE157050_AATSC_insmet_PvsI.edgeR.txt.gz |
261.9 Kb |
(ftp)(http) |
TXT |
| GSE157050_AATSC_met_PvsI.edgeR.txt.gz |
259.9 Kb |
(ftp)(http) |
TXT |
| GSE157050_AATSC_ut_PvsI.edgeR.txt.gz |
260.2 Kb |
(ftp)(http) |
TXT |
| GSE157050_AA_ins_PvsI.edgeR.txt.gz |
262.5 Kb |
(ftp)(http) |
TXT |
| GSE157050_AA_insmet_PvsI.edgeR.txt.gz |
260.3 Kb |
(ftp)(http) |
TXT |
| GSE157050_AA_met_PvsI.edgeR.txt.gz |
259.5 Kb |
(ftp)(http) |
TXT |
| GSE157050_AA_ut_PvsI.edgeR.txt.gz |
259.6 Kb |
(ftp)(http) |
TXT |
| GSE157050_AMPK_ins_PvsI.edgeR.txt.gz |
261.6 Kb |
(ftp)(http) |
TXT |
| GSE157050_AMPK_insmet_PvsI.edgeR.txt.gz |
261.1 Kb |
(ftp)(http) |
TXT |
| GSE157050_AMPK_met_PvsI.edgeR.txt.gz |
260.2 Kb |
(ftp)(http) |
TXT |
| GSE157050_AMPK_ut_PvsI.edgeR.txt.gz |
259.9 Kb |
(ftp)(http) |
TXT |
| GSE157050_TSC_ins_PvsI.edgeR.txt.gz |
262.1 Kb |
(ftp)(http) |
TXT |
| GSE157050_TSC_insmet_PvsI.edgeR.txt.gz |
261.8 Kb |
(ftp)(http) |
TXT |
| GSE157050_TSC_met_PvsI.edgeR.txt.gz |
260.3 Kb |
(ftp)(http) |
TXT |
| GSE157050_TSC_ut_PvsI.edgeR.txt.gz |
260.5 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_ink_PvsI.edgeR.txt.gz |
262.3 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_ins_PvsI.edgeR.txt.gz |
262.3 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_insink_PvsI.edgeR.txt.gz |
260.0 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_insmet_PvsI.edgeR.txt.gz |
261.8 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_met_PvsI.edgeR.txt.gz |
260.6 Kb |
(ftp)(http) |
TXT |
| GSE157050_WT_ut_PvsI.edgeR.txt.gz |
261.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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