Abstract

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 mammalian cells via amino acid transporters and thus the expression and activity of these transporters likely influences 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 transporter LAT1 is abundantly expressed
in islets and that knock-down of LAT1 using siRNA inhibits mTORC1 signalling, leucine-stimulated
insulin secretion and islet cell proliferation. In summary, we show that the System-L transporter
LAT1 is required for regulating β-cell signaling and function in islets and thus may be a novel
pharmacological/nutritional target for the treatment and prevention of type-2 diabetes.