Alterations of the glutamatergic system in diabetes mellitus

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels caused by a lack of insulin production (type 1 diabetes) or insulin resistance (type 2 diabetes). It is well known that DM is associated with cognitive deficits and metabolic and neurophysiological changes in the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system that plays a key role in synaptic plasticity, learning, and memory processes. An increasing number of studies have suggested that abnormal activity of the glutamatergic system is implicated in the pathophysiology of DM. Dysfunction of glutamatergic neurotransmission in the central nervous system can provide an important neurobiological substrate for many disorders. Magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows a better understanding of the central nervous system factors by measuring in vivo the concentrations of brain metabolites within the area of interest. Here, we briefly review the MRS studies that have examined glutamate levels in the brain of patients with DM. The present article also summarizes the available data on abnormalities in glutamatergic neurotransmission observed in different animal models of DM. In addition, the role of gut microbiota in the development of glutamatergic alterations in DM is addressed. We speculate that therapeutic strategies targeting the glutamatergic system may be beneficial in the treatment of central nervous system-related changes in diabetic patients.