|
| Status |
Public on May 01, 2017 |
| Title |
Amino Acid Transporter Slc38a5 Mediates Glucagon Receptor Inhibition-Induced Pancreatic α-Cell Hyperplasia in Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids, and compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Regulation of pancreatic α- and β-cell growth has drawn a lot of attention because of potential therapeutic implications. Recent findings indicate that hyperaminoacidemia triggers pancreatic α-cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α-cells, and that Slc38a5 is critical for the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α-cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino acid-dependent regulation of pancreatic α-cell mass in mice.
|
| |
|
| Overall design |
Examination of the transcriptomes of pancreatic islets of mice treated with GCGR-antibody and an isotype control antibody.
|
| |
|
| Contributor(s) |
Kim J, Gromada J |
| Citation(s) |
28591637 |
| |
| Submission date |
Nov 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Yurong Xin |
| E-mail(s) |
yurong.xin@regeneron.com
|
| Organization name |
Regeneron Pharmaceuticals, Inc.
|
| Street address |
777 Old Saw Mill River Road
|
| City |
Tarrytown |
| State/province |
NY |
| ZIP/Postal code |
10598 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (10)
|
| GSM2385840 |
Sample_4_Pancreatic islets_R1193 |
| GSM2385841 |
Sample_5_Pancreatic islets_R1193 |
| GSM2385842 |
Sample_6_Pancreatic islets_isotype_control |
| GSM2385843 |
Sample_7_Pancreatic islets_isotype_control |
| GSM2385844 |
Sample_8_Pancreatic islets_isotype_control |
| GSM2385845 |
Sample_9_Pancreatic islets_isotype_control |
| GSM2385846 |
Sample_10_Pancreatic islets_isotype_control |
|
| Relations |
| BioProject |
PRJNA352756 |
| SRA |
SRP092805 |
Less...
More...