Differential Expression of the Glutamate Transporter GLT-1 in Pancreas

Abstract

SummaryThe glutamate uptake transporter GLT-1 is best understood for its critical role in preventing brain seizures. Increasing evidence argues that GLT-1 also modulates, and is modulated by, metabolic processes that influence glucose homeostasis. To investigate further the potential role of GLT-1 in these regards, the authors examined GLT-1 expression in pancreas and found that mature multimeric GLT-1 protein is stably expressed in the pancreas of wild-type, but not GLT-1 knockout, mice. There are three primary functional carboxyl-terminus GLT-1 splice variants, called GLT-1a, b, and c. Brain and liver express all three variants; however, the pancreas expresses GLT-1a and GLT-1b but not GLT-1c. Quantitative real time-PCR further revealed that while GLT-1a is the predominant GLT-1 splice variant in brain and liver, GLT-1b is the most abundant splice variant expressed in pancreas. Confocal microscopy and immunohistochemistry showed that GLT-1a and GLT-1b are expressed in both islet β-and α-cells. GLT-1b was also expressed in exocrine ductal domains. Finally, glutamine synthetase was coexpressed with GLT-1 in islets, which suggests that, as with liver and brain, one possible role of GLT-1 in the pancreas is to support glutamine synthesis. (J Histochem Cytochem 60:139-151, 2012)

Partial Loss of the Glutamate Transporter GLT-1 Alters Brain Akt and Insulin Signaling in a Mouse Model of Alzheimer's Disease

“…GLT-1 is expressed at low levels in the pancreas [65], thereby raising the question whether some aspects of GLT-1 function might be related to pancreatic GLT-1 endocrine and/or exocrine activity. However, recent studies using mice with a brain-specific GLT-1 deficiency demonstrate that GLT-1 loss in the brain alone is sufficient to account for the primary phenotypes associated with total systemic GLT-1 loss [1, 66].…”

“…In conjunction with reduced brain IDE activity, GLT-1 loss also caused a marked increase in IDE activity in the liver, which expresses high levels of GLT-1 in zone 3 hepatocytes [65, 72]. While we found a significant increase in the ratio of Aβ 42 /Aβ 40 in these mice at 6 months of age, we did not find any other significant changes in Aβ accumulation between the GLT wt /AβPP/PS1 and GLT het /AβPP/PS1 groups at either 6 or 9 months [20].…”

Blast Exposure Causes Early and Persistent Aberrant Phospho- and Cleaved-Tau Expression in a Murine Model of Mild Blast-Induced Traumatic Brain Injury

“…Tissue lysates for western blot analyses were then prepared as previously described [22] with the following minor modifications: phosphatase inhibitor cocktail sets 2 and 3 (Sigma, St. Louis, MO) were added (10 μ/ml) to the lysis buffer and tissues were homogenized twice by hand using an Eppendorf tube-fitting pestle (Eppendorf, Hauppauge, NY) before centrifuge clarification. Criterion 4–20% TGX gels (Bio-Rad, Hercules, CA) were loaded with 20 μg/lane and probed only once after overnight incubation (4 C) with the following antibodies: AT8, AT100, AT270 (from Thermo Scientific, Waltham, MA); Tau-5, TauC3, anti-phospho-tau 396 (from Life Technologies, Grand Island, NY); CP13, and PHF-1 (gifts from Peter Davies); rabbit polyclonal pan-tau antibodies (gift from Virginia Lee); SOD2, AβPP, and GFAP (from EMD Millipore, Billerica, MA).…”

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

“…However, as * This work was supported by the Norwegian Research Council (Centre of summarized in Table 1, there is a great deal of uncertainty. Some investigators have reported expression in the plasma membranes but have arrived at different conclusions with respect to cell types and functional roles (10,(22)(23)(24)(25). Another study (26) proposed a radically new model in which EAAT2 colocalizes with the VGLUT3 in the membranes of insulincontaining secretory granules.…”