While extracellular glutamic acid is an excitatory neurotransmitter, intracellular glutamic acid is an amino acid that serves numerous metabolic roles. Dimethyl DL-glutamate is a cell-permeant glutamic acid derivative that enhances insulin release in response to glucose in isolated islets and in animal models of diabetes. It also potentiates the insulinotropic potential of glyburide and glucagon-like peptide 1. Dimethyl DL-glutamate is used as a cell-permeable form of glutamate in studies of glutamate action in β-cells. However, it can be cytotoxic to myeloid cells and act as an antagonist of glutamate-mediated neurosignaling.
While extracellular glutamic acid is an excitatory neurotransmitter, intracellular glutamic acid is an amino acid that serves numerous metabolic roles. Dimethyl DL-glutamate Hydrochloride is a cell-permeant glutamic acid derivative that enhances insulin release in response to glucose in isolated islets and in animal models of diabetes. It also potentiates the insulinotropic potential of glyburide and glucagon-like peptide 1. Dimethyl DL-glutamate Hydrochloride is used as a cell-permeable form of glutamate in studies of glutamate action in β-cells. However, it can be cytotoxic to myeloid cells and act as an antagonist of glutamate-mediated neurosignaling.
dimethyl dl-glutamate at 3.0-10.0 mm could enhance insulin release evoked by 6.0-8.3 mm d-glucose, 1.0-10.0 mm l-leucine, or 5.0-10.0 mm 2-amino-bicyclo(2,2,1)heptane-2-carboxylic acid, resulting in a shift to the left of the sigmoidal relationship between insulin output and d-glucose concentration. moreover, dimethyl dl-glutamate unmasked the insulinotropic potential of glibenclamide in the absence of d-glucose. in islets exposed to l-leucine, the insulinotropic action of dimethyl dl-glutamate coincided with an early fall and later increase in 86rb outflow. in addition, the overall gain in o2 uptake represented the balance between dimethyl dl-glutamate oxidation and its sparing action on the catabolism of endogenous fatty acids and exogenous d-glucose [1].
dimethyl dl-glutamate was intravenously administered as a primed constant infusion to adult rats that had been injected with streptozotocin during the neonatal period. results showed that dimethyl dl-glutamate augmented plasma insulin concentration and potentiated and/or prolonged the insulinotropic action of glp-1 injected intravenously at min 5 of the test [2].
[1] sener, a. ,conget, i.,rasschaert, j., et al. insulinotropic action of glutamic acid dimethyl ester. american journal of physiology 267(4 pt 1), e573-e584 (1994).
[2] cancelas, j. ,villaneuva-peacarrillo, m.l.,valverde, i., et al. potentiation and prolongation of the insulinotropic action of glucagon-like peptide 1 by methyl pyruvate or dimethyl ester of l-glutamic acid in a type 2 diabetes animal model. endocrine 16(2), 113-116 (2001).
