Expression of the electrogenic Na+-HCO3--cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells.
It was recently proposed that, in rat pancreatic islets, the production of bicarbonate accounts for the major fraction of the carbon dioxide generated by the oxidative catabolism of nutrient insulin secretagogues. In search of the mechanism(s) supporting the membrane transport of bicarbonate, the possible role of the electrogenic Na(+)-HCO(3) (-)-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells was investigated. Expression of NBCe1-A and NBCe1-B in rat pancreatic islet cells was documented by RT-PCR, western blotting, and immunocytochemistry. The latter procedure suggested a preferential localization of NBCe1-B in insulin-producing cells. Tenidap (3-100 microM), previously proposed as an inhibitor of NBCe1-A-mediated cotransport in proximal tubule kidney cells, caused a concentration-related inhibition of glucose-stimulated insulin secretion. It also inhibited 2-ketoisocaproate-induced insulin release and to a relatively lesser extent, the secretory response to L: -leucine. Tenidap (50-100 microM) also inhibited the metabolism of D: -glucose in isolated islets, increased (22)Na net uptake by dispersed islet cells, lowered intracellular pH and provoked hyperpolarization of plasma membrane in insulin-producing cells. This study thus reveals the expression of the electrogenic Na(+)-HCO(3) (-)-cotransporters NBCe1-A and NBCe1-B in rat pancreatic islet cells, and is consistent with the participation of such transporters in the process of nutrient-stimulated insulin secretion.
Soyfoo
Muhammad S
MS
Laboratory of Biological Chemistry and Nutrition, Université Libre de Bruxelles, Brussels, Belgium.
Bulur
Nurdan
N
Virreira
Myrna
M
Louchami
Karim
K
Lybaert
Pascale
P
Crutzen
Raphael
R
Perret
Jason
J
Delporte
Christine
C
Roussa
Eleni
E
Thevenod
Frank
F
Best
Len
L
Yates
Allen P
AP
Malaisse
Willy J
WJ
Sener
Abdullah
A
Beauwens
Renaud
R
D000818:Animals; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D007328:Insulin; D020033:Protein Isoforms; C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters; D012964:Sodium; D005947:Glucose