in this issue of Cell Metabolism, provide evidence that glutamate can act as a positive autocrine signal for a cell glucagon release in pri mates (human and monkey) and mice. Employing a variety of elegant experimental approaches, they show that glutamate is indeed secreted by a cell in response to low glucose concentration. Moreover, the secreted glutamate acts in a positive autocrine manner in vitro and in vivo through a cell ionotropic glutamate receptor (iGluRs).