The Glial Glutamate Transporter 1 (GLT1) Is Expressed by Pancreatic β-Cells and Prevents Glutamate-induced β-Cell Death*

  title={The Glial Glutamate Transporter 1 (GLT1) Is Expressed by Pancreatic $\beta$-Cells and Prevents Glutamate-induced $\beta$-Cell Death*},
  author={Eliana Sara Di Cairano and Alberto M. Davalli and Lucia Perego and Silvia Sala and Vellea Franca Sacchi and Stefano La Rosa and Giovanna Finzi and Claudia Placidi and Carlo Renato Capella and Paola Conti and Victoria E. Centonze and Francesca Casiraghi and Federico Bertuzzi and Franco Folli and Carla Perego},
  journal={The Journal of Biological Chemistry},
  pages={14007 - 14018}
Glutamate is the major excitatory neurotransmitter of the central nervous system (CNS) and may induce cytotoxicity through persistent activation of glutamate receptors and oxidative stress. Its extracellular concentration is maintained at physiological concentrations by high affinity glutamate transporters of the solute carrier 1 family (SLC1). Glutamate is also present in islet of Langerhans where it is secreted by the α-cells and acts as a signaling molecule to modulate hormone secretion… 

Figures from this paper

Diabetes: Pathogenesis of diabetes mellitus: does glutamate have a role?

Glial glutamate transporter 1 (GLT1) is expressed in pancreatic β cells and acts as a critical regulator of extracellular glutamate levels, which in turn promotes β-cell survival, report researchers

High glucose stimulates glutamate uptakes in pancreatic β-cells

Investigation of the effect of high glucose on glutamate uptake in pancreatic β-cells found that high glucose stimulated glutamate uptake via oxidative stress in pancreato-cells via N-acetyl-L-cysteine and quercetin.

Role of NMDA Receptors in Pancreatic Islets

It is hypothesized that NMDARs on β-cells are permanently occupied by glutamate derived from the leaky, fenestrated blood capillary network of the islets, and that N-methyl-d-aspartate receptors activity is mainly induced by depolarization of theβ-cells, which explains why deletion of N MDARs only increases insulin release from β- cells when blood glucose concentrations are high and β- Cells are depolarized.

The Amino Acid Transporters of the Glutamate/GABA-Glutamine Cycle and Their Impact on Insulin and Glucagon Secretion

High levels of glutamate, GABA, and glutamine and their respective vesicular and plasma membrane transporters have been shown in the islet cells and there is emerging support for these amino acids and their transporter playing important roles in the maturation and secretion of insulin and glucagon.

Exciting Times for Pancreatic Islets: Glutamate Signaling in Endocrine Cells

Proteome Analysis and Conditional Deletion of the EAAT2 Glutamate Transporter Provide Evidence against a Role of EAAT2 in Pancreatic Insulin Secretion in Mice*

The EAAT2 levels were found to be too low to support any of the four hypothesized functions, which suggests that the uptake of glutamate by islets from the extracellular fluid is insignificant and that glutamate is intracellularly produced.

Characterization of pancreatic NMDA receptors as possible drug targets for diabetes treatment

In a mouse model of type 2 diabetes mellitus (T2DM), long-term treatment withDXM improved islet insulin content, islet cell mass and blood glucose control and in a small clinical trial it was found that individuals with T2DM treated with DXM showed enhanced serum insulin concentrations and glucose tolerance.



Human T Cells Express a Functional Ionotropic Glutamate Receptor GluR3, and Glutamate by Itself Triggers Integrin-Mediated Adhesion to Laminin and Fibronectin and Chemotactic Migration1

The discovery that normal human T cells, human T leukemia cells, and mouse anti-myelin basic protein T cells express high levels of glutamate ion channel receptor (ionotropic) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype 3 (GluR3) reveals a novel peripheral source of this antigenic receptor.

The GLT‐1 and GLAST Glutamate Transporters Are Expressed on Morphologically Distinct Astrocytes and Regulated by Neuronal Activity in Primary Hippocampal Cocultures

The data indicate that soluble factors dependent on neuronal activity play a major regulating role in hippocampal cocultures and soluble factors in neuronal‐conditioned media prevented the down‐regulation of the GLT‐1 and GLAST proteins.

Mechanism of Ceftriaxone Induction of Excitatory Amino Acid Transporter-2 Expression and Glutamate Uptake in Primary Human Astrocytes*

The data indicate that ceftriaxone is a potent modulator of glutamate transport in PHFA through NF-κB-mediated EAAT2 promoter activation, and suggest a mechanism for ceftRIaxone modulation of glutamate Transport and for its potential effects on ameliorating specific neurodegenerative diseases through modulation of extracellular glutamate.

β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression

Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, it is discovered that many β-lactam antibiotics are potent stimulators of GLT1 expression, and this action appears to be mediated through increased transcription of theGLT1 gene.

A High Affinity Glutamate/Aspartate Transport System in Pancreatic Islets of Langerhans Modulates Glucose-stimulated Insulin Secretion*

Data suggest that a high affinity glutamate transport system exists in pancreatic islets and that this system contributes to a glutamatergic signaling pathway that can modulate glucose-inducible insulin secretion.

Secretory Granule-mediated Co-secretion ofl-Glutamate and Glucagon Triggers Glutamatergic Signal Transmission in Islets of Langerhans*

Results indicate that co-secretion ofl-glutamate and glucagon from α cells under low glucose conditions triggers GABA secretion from β cells and defines the mode of action of l- glutamate as a regulatory molecule for the endocrine function.

Metabotropic glutamate receptor type 4 is involved in autoinhibitory cascade for glucagon secretion by alpha-cells of islet of Langerhans.

Results indicate that alpha- and F cells express functional mGluR4, and its stimulation inhibits secretion of glucagon through an inhibitory cAMP cascade, indicating that L-glutamate may directly interact with alpha-cells and inhibit glucagon secretion.

Metabotropic glutamate and GABAB receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells

Data suggest that mGluRs and GABABRs play a role in the regulation of the endocrine pancreas with mechanisms probably involving direct activation or inhibition of voltage dependent Ca2+-channels, cAMP generation and G-protein-mediated modulation of KATP channels.