| First Author | Kim J | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 6 | Pages | 1348-1361.e8 |
| PubMed ID | 28591637 | Mgi Jnum | J:251829 |
| Mgi Id | MGI:6106811 | Doi | 10.1016/j.cmet.2017.05.006 |
| Citation | Kim J, et al. (2017) Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic alpha Cell Hyperplasia in Mice. Cell Metab 25(6):1348-1361.e8 |
| abstractText | 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 alpha cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic alpha 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 alpha cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased alpha 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 alpha cell mass in mice. |
