Pancreatic islet α cell function and proliferation requires the arginine transporter SLC7A2.

Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood resulting in lower glycemia. The resulting hyperaminoacidemia stimulates α cell proliferation and glucagon secretion via a liver-α cell axis. We hypothesized that α cells detect and respond to circulating amino acids levels via a unique amino acid transporter repertoire. We found that