دورية أكاديمية
System-L amino acid transporters play a key role in pancreatic β-cell signalling and function.
| العنوان: | System-L amino acid transporters play a key role in pancreatic β-cell signalling and function. |
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| المؤلفون: | Cheng Q; Research School of BiologyAustralian National University, Acton, Australia., Beltran VD; Department of InfectionImmunity and Inflammation, University of Leicester, UK., Chan SM; Health Innovations Research Institute (HIRI)School of Medical Sciences, RMIT University, Bundoora, Australia., Brown JR; Department of InfectionImmunity and Inflammation, University of Leicester, UK., Bevington A; Department of InfectionImmunity and Inflammation, University of Leicester, UK., Herbert TP; Health Innovations Research Institute (HIRI)School of Medical Sciences, RMIT University, Bundoora, Australia terence.herbert@rmit.edu.au. |
| المصدر: | Journal of molecular endocrinology [J Mol Endocrinol] 2016 Apr; Vol. 56 (3), pp. 175-87. Date of Electronic Publication: 2015 Dec 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioScientifica Country of Publication: England NLM ID: 8902617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1479-6813 (Electronic) Linking ISSN: 09525041 NLM ISO Abbreviation: J Mol Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Bristol, U.K. : Journal of Endocrinology, Ltd., c1988- |
| مواضيع طبية MeSH: | Signal Transduction*, Amino Acid Transport System L/*metabolism , Insulin-Secreting Cells/*metabolism, Amino Acid Transport System L/genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression ; Insulin/metabolism ; Islets of Langerhans/metabolism ; Large Neutral Amino Acid-Transporter 1/metabolism ; Leucine/metabolism ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Multiprotein Complexes/metabolism ; Rats ; TOR Serine-Threonine Kinases/metabolism |
| مستخلص: | The branched-chain amino acids (BCAA) leucine, isoleucine and valine, are essential amino acids that play a critical role in cellular signalling and metabolism. They acutely stimulate insulin secretion and activate the regulatory serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1), a kinase that promotes increased β-cell mass and function. The effects of BCAA on cellular function are dependent on their active transport into the mammalian cells via amino acid transporters and thus the expression and activity of these transporters likely influence β-cell signalling and function. In this report, we show that the System-L transporters are required for BCAA uptake into clonal β-cell lines and pancreatic islets, and that these are essential for signalling to mTORC1. Further investigation revealed that the System-L amino acid transporter 1 (LAT1) is abundantly expressed in the islets, and that knockdown of LAT1 using siRNA inhibits mTORC1 signalling, leucine-stimulated insulin secretion and islet cell proliferation. In summary, we show that the LAT1 is required for regulating β-cell signalling and function in islets and thus may be a novel pharmacological/nutritional target for the treatment and prevention of type 2 diabetes. (© 2016 Society for Endocrinology.) |
| فهرسة مساهمة: | Keywords: amino acid transporters; cellular signalling; diabetes; islets; mTORC1 |
| المشرفين على المادة: | 0 (Amino Acid Transport System L) 0 (Insulin) 0 (Large Neutral Amino Acid-Transporter 1) 0 (Multiprotein Complexes) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) EC 2.7.11.1 (TOR Serine-Threonine Kinases) GMW67QNF9C (Leucine) |
| تواريخ الأحداث: | Date Created: 20151210 Date Completed: 20171026 Latest Revision: 20211204 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1530/JME-15-0212 |
| PMID: | 26647387 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-6813 |
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| DOI: | 10.1530/JME-15-0212 |