Expression of the Electrogenic Na+-HCO3--Cotransporter NBCe1 in Tumoral Insulin-Producing BRIN-BD11 Cells

Abstract

Background/aims: The expression of the electrogenic Na⁺-HCO₃^--cotransporter NBCe1 was recently documented in rat pancreatic islet B-cells, it being speculated that such a protein participates in the extrusion of bicarbonate generated by the oxidative catabolism of nutrients from insulin-producing cells. Considering the prevalence of a Crabtree effect in tumoral insulin-producing cells, the possible presence of NBCe1 was now investigated in BRIN-BD11 cells, an insulin-producing cell line established by electrofusion of normal pancreatic B-cells with immortalized RINm5F cells. Methods: The possible presence of NBCe1 in BRIN-BD11 cells was investigated by RT-PCR, western blot analysis and immunocytochemistry. The release of insulin and net uptake of ²²Na⁺ were also measured in the BRIN-BD11 cells. Results: RT-PCR, western blot analysis and immunocytochemistry documented the presence of NBCe1 in BRIN-BD11 cells. A reported inhibitor of NBCe1, i.e. tenidap, (50-100 μM), inhibited basal and hypotonicity-induced insulin release from the BRIN-BD11 cells, whilst increasing the net uptake of ²²Na⁺ by the same cells. The latter effect was, in relative terms, more pronounced in the presence than absence of ouabain. Conclusion: BRIN-BD11 cells, like normal pancreatic islet B-cells, express NBCe1, with predominance of the B variant of this electrogenic Na⁺-HCO₃^--cotransporter.