The glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging.

Mol Metab. (2019)

Abarkan M, Gaitan J, Lebreton F, Perrier R, Jaffredo M, Mulle C, Magnan C, Raoux M, Lang J

Islets secrete neurotransmitters including glutamate which participate in fine regulation of islet function. The excitatory ionotropic glutamate receptor GluK2 of the kainate receptor family is widely expressed in brain and also found in islets, mainly in α and γ cells. α cells co-release glucagon and glutamate and the latter increases glucagon release via ionotropic glutamate receptors. However, neither the precise nature of the ionotropic glutamate receptor involved nor its role in glucose homeostasis is known. As isoform specific pharmacology is not available, we investigated this question in constitutive GluK2 knock-out mice (GluK2^-/-) using adult and middle-aged animals to also gain insight in a potential role during aging.

Our observations indicate a general role for kainate receptors in glucose homeostasis and specifically suggest a negative effect of GluK2 on glucose homeostasis and preservation of islet function during aging. These observations raise the possibility that blockade of GluK2 may provide benefits in glucose homeostasis especially during aging.