Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice
| Autor: | Guillermo Anguiano, Brian Zambrowicz, Haruka Okamoto, Wen Hong Li, Jesper Gromada, Jinrang Kim, Shiuhwei Chen, Erqian Na, Qing Liu, George D. Yancopoulos, Joseph Lee, Yurong Xin, Zhi Jiang Huang, Roger H Unger, Katie Cavino, Yan Xu, Rachid Hamid, Andrew J. Murphy |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Physiology Glucagon Article 03 medical and health sciences Mice Internal medicine medicine Receptors Glucagon Glucose homeostasis Animals Amino acid transporter Molecular Biology Glucagon-like peptide 1 receptor chemistry.chemical_classification Mice Knockout Mice Inbred ICR Hyperplasia Chemistry Cell Biology medicine.disease Amino acid 030104 developmental biology Endocrinology Amino Acid Transport Systems Neutral Glucagon-Secreting Cells Hyperaminoacidemia Glucagon receptor Glucagon receptor family Signal Transduction |
| Zdroj: | Cell Metab |
| Popis: | 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. 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 controls 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. |
| Databáze: | OpenAIRE |
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