Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge, Mass. : Cell Press, c2005-
    • Subject Terms:
      Signal Transduction*; Amino Acid Transport Systems, Neutral/*metabolism ; Glucagon/*metabolism ; Glucagon-Secreting Cells/*metabolism ; Receptors, Glucagon/*metabolism; Amino Acid Transport Systems, Neutral/genetics ; Animals ; Glucagon/genetics ; Glucagon-Secreting Cells/pathology ; Hyperplasia ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Receptors, Glucagon/genetics
    • Abstract:
      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.
      (Copyright © 2017 Elsevier Inc. All rights reserved.)
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    • Grant Information:
      R01 GM077593 United States GM NIGMS NIH HHS
    • Contributed Indexing:
      Keywords: Slc38a5; amino acid transporter; glucagon; glucagon receptor; glucagon receptor knockout; hyperaminoacidemia; mTORC1; pancreatic alpha cell; proliferation
    • Accession Number:
      0 (Amino Acid Transport Systems, Neutral)
      0 (Receptors, Glucagon)
      0 (SNAT5 protein, mouse)
      9007-92-5 (Glucagon)
    • Publication Date:
      Date Created: 20170608 Date Completed: 20180309 Latest Revision: 20210617
    • Publication Date:
      20221213
    • Accession Number:
      PMC8206958
    • Accession Number:
      10.1016/j.cmet.2017.05.006
    • Accession Number:
      28591637