Dimethyl DL-Glutamate (hydrochloride)

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Background

Dimethyl DL-glutamate is a cell-permeable form of glutamate.
Extracellular glutamic acid is an excitatory neurotransmitter, while intracellular glutamic acid is an amino acid that serves various metabolic roles.
In vitro: 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].
In vivo: 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].
Clinical trial: So far, no clinical study has been conducted.

[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).