The system-L amino acid transporter LAT1 couples to the regulatory kinase mTORC1 to stimulate both beta-cell function and proliferation. — ASN Events
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The system-L amino acid transporter LAT1 couples to the regulatory kinase mTORC1 to stimulate both beta-cell function and proliferation. (#220)

Qi Cheng 1 , Violeta D Beltran 2 , Stanley Chan 3 , Alan Bevington 2 , Terence P Herbert 3
  1. Biomedical Science and Biochemistry, The Australian National University, Acton, ACT, Australia
  2. Leicester University, Leicester, UK
  3. RMIT, Bundoora, VIC, Australia

The branched-chain amino acids (BCAA) leucine, isoleucine and valine, are essential amino acids that play a critical role in cellular signaling 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 beta-cell mass and function. The effects of BCAA on cellular function are dependent on their active transport into mammalian cells. Thus amino acid transporter expression and activity are undoubtedly important mediators of beta-cell signaling and function.

The aims of this study were to identify the transporters responsible for BCAA uptake into beta-cells and to investigate their role in regulating beta-cell function and mass.

Our data provides evidence that the System-L family of amino acid transporters is required for BCAA uptake into both clonal beta-cell lines and pancreatic islets. We show that these are essential for signaling to mTORC1, leucine-stimulated insulin secretion and islet cell proliferation. Further investigation revealed that LAT1 is the most abundantly expressed System-L transporter in islets. knock-down of LAT1 using siRNA demonstrated that it plays a significant role in maintaining beta-cell signaling, function and proliferation.

In summary, we show that the System-L transporter LAT1 is required for regulating beta-cell signaling and function in islets and thus may be a novel pharmacological/nutritional target for the treatment and/or even the prevention of type-2 diabetes.