Increasing evidence suggests that the excitatory neurotransmitter L-glutamate functions as a modulator in the islet of Langerhans, an endocrine organ involved in blood glucose homeostasis. It is release by α-cells and, by acting on specific receptors, it modulates hormone secretion and β-cell mass. Its extracellular concentration is mainly controlled by the glutamate transporter GLT1 which is expressed on the plasma membrane of β-cells (Di Cairano et al, JBC 2011; 286: 14007). Aim of the proposed research was to verify the impact of acute and chronic changes in glucose concentrations on GLT1 localization/function and glutamate signalling in the islet. We found that acute exposure of human and clonal β-cells to high glucose concentrations (15 mM glucose) inhibited the GLT1 transport activity measured by [3H]D-glutamate uptake, in a dose-dependent manner. Furthermore, total internal reflection microscopy experiments performed on β-cells transfected with a GFP-GLT1 tagged transporter demonstrated that glucose stimulation decreased the surface stability of GLT1 and increased its endocytosis. Chronic exposure of human and clonal β-cells to high glucose concentrations caused the GLT1 relocalization in degradative compartments and significantly reduced its total expression. Interestingly, a similar intracellular GLT1 staining was detected in human islets from type 2 diabetic donors (n=8) but not from healthy controls (n=5). Understanding the molecular mechanisms that control glutamate release and signalling in islet of Langerhans may be important to control glucose homeostasis in health and disease.

The glutamate signalling in islet of Langerhans: molecular mechanisms of modulation / C. Perego, S. Moretti, E. Di Cairano, D. Mengacci, F. Daniele, S. Larosa, F. Bertuzzi, F. Folli. ((Intervento presentato al 64. convegno Congress of the Italian Physiological Society tenutosi a Portonovo nel 2013.

The glutamate signalling in islet of Langerhans: molecular mechanisms of modulation

C. Perego;S. Moretti;E. Di Cairano;F. Folli
2014-09

Abstract

Increasing evidence suggests that the excitatory neurotransmitter L-glutamate functions as a modulator in the islet of Langerhans, an endocrine organ involved in blood glucose homeostasis. It is release by α-cells and, by acting on specific receptors, it modulates hormone secretion and β-cell mass. Its extracellular concentration is mainly controlled by the glutamate transporter GLT1 which is expressed on the plasma membrane of β-cells (Di Cairano et al, JBC 2011; 286: 14007). Aim of the proposed research was to verify the impact of acute and chronic changes in glucose concentrations on GLT1 localization/function and glutamate signalling in the islet. We found that acute exposure of human and clonal β-cells to high glucose concentrations (15 mM glucose) inhibited the GLT1 transport activity measured by [3H]D-glutamate uptake, in a dose-dependent manner. Furthermore, total internal reflection microscopy experiments performed on β-cells transfected with a GFP-GLT1 tagged transporter demonstrated that glucose stimulation decreased the surface stability of GLT1 and increased its endocytosis. Chronic exposure of human and clonal β-cells to high glucose concentrations caused the GLT1 relocalization in degradative compartments and significantly reduced its total expression. Interestingly, a similar intracellular GLT1 staining was detected in human islets from type 2 diabetic donors (n=8) but not from healthy controls (n=5). Understanding the molecular mechanisms that control glutamate release and signalling in islet of Langerhans may be important to control glucose homeostasis in health and disease.
Islets of Langerhans ; glutamate ; transporter ; diabetes
Settore BIO/09 - Fisiologia
Settore MED/13 - Endocrinologia
The glutamate signalling in islet of Langerhans: molecular mechanisms of modulation / C. Perego, S. Moretti, E. Di Cairano, D. Mengacci, F. Daniele, S. Larosa, F. Bertuzzi, F. Folli. ((Intervento presentato al 64. convegno Congress of the Italian Physiological Society tenutosi a Portonovo nel 2013.
Conference Object
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/237808
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact