Glutamate-mediated signaling in the islets of Langerhans: A thread entangled

Increasing evidence suggests that the excitatory neurotransmitter L-glutamate functions as a modulator in the islet of Langerhans, an endocrine organ involved in blood glucose homeostasis. The islet is equipped with all the elements required for L-glutamate-mediated transmission, and it has been shown that L-glutamate is co-stored and co-secreted with glucagon from α-cells following treatment with low levels of glucose, and triggers the secondary paracrine response of islet cells. In this article, we propose that L-glutamate regulates the secretion of glucagon from islets but does not affect the secretion of insulin from islets. It is suggested that the effects of glutamate are mediated by the activation of GABA_A receptors on α-cells following glutamate-mediated release of GABA from β-cells and the activation of glutamate receptors on α-cells. This novel regulatory mechanism for islet hormone secretion should provide a target for chemotherapeutics in the treatment of class II diabetes mellitus.