L-Glutamate is the major excitatory neurotransmitter in the central nervous system and plays important roles in many neuronal processes such as fast synaptic transmission and neuronal plasticity (1, 2). To use L-glutamate as an intercellular signaling molecule, neuronal cells develop the glutamatergic system. Thus, L-glutamate is accumulated in synaptic vesicles through vesicular glutamate transporters (VGLUTs), 1 and is secreted through exocytosis. The released L-glutamate binds to the receptor so as to transmit signals intercellularly. The excess amount of L-glutamate in synaptic cleft is sequestrated through plasma membrane-type glutamate transporter. Recent evidence has indicated that peripheral non-neuronal tissues also possess the glutamatergic system and use L-glutamate as an intercellular transmitter (3). The islet of Langerhans, a pancreatic miniature organ for the hormones regulating the blood glucose level, is composed of four major types of endocrine cells, i.e. insulin-secreting  cells, glucagon-secreting ␣ cells, somatostatin-secreting ␦ cells, and pancreatic polypeptide-secreting F cells. These islet cells expresses functional glutamate receptors and plasma membrane-type glutamate transporter (4 -11), suggesting that L-glutamate functions as an intercellular transmitter in islet. In fact, L-glutamate has been shown to affect secretion of insulin or glucagon from islet cells, isolated islets, or perfused pancreas (4 -11). However, the role of L-glutamate as an intercellular chemical transmitter in the islets has been long controversial, mainly because critical issues, i.e. where, when, and how L-glutamate appears in the islets and what happens upon stimulation of glutamate receptors in the islets, remain unresolved.Recent findings indicate that brain-specific Na ϩ -dependent inorganic phosphate cotransporter (12) and its isoform, differentiation-associated Na ϩ -dependent inorganic phosphate cotransporter (13), function as VGLUTs and are thus abbreviated as VGLUT1 and VGLUT2, respectively (14 -21). These VGLUTs seem to be potential probes for the site of L-glutamate release in peripheral tissues as well as the central nervous system since these transporters are essential for L-glutamate signal output. We have shown that VGLUT2 is expressed in ␣TC6 cells, clonal ␣ cells, and islet ␣ cells, but not in  or ␦ cells (18). These results are consistent with the occurrence of Ca 2ϩ -dependent exocytosis of L-glutamate from ␣TC6 cells (22) and suggest that ␣ cells are the sites of L-glutamate signal appearance.During course of the study, we noticed that the expression and subcellular localization of VGLUTs are of extraordinary
