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Low serum bicarbonate is closely related to type 2 diabetes mellitus. However, the precise role of bicarbonate on glucose homeostasis and insulin secretion remains unknown. In this study, we investigated the effects of bicarbonate concentration on pancreatic β-cells. It was observed that the high bicarbonate concentration of the cell culture medium significantly increased the glucose-induced insulin secretion (GSIS) levels in mouse islets, MIN6, and the INS-1E β cells. MIN6 cells presented an impaired GSIS; the cells produced a lower bicarbonate concentration when co-cultured with Capan-1 than when with CFPAC-1. NBCe1, a major bicarbonate transporter was observed to block the increasing insulin secretions, which were promoted by a high concentration of bicarbonate. In addition, higher extracellular bicarbonate concentration significantly increased the intracellular cAMP level, pHi, and calcium concentration with a 16.7 mM of glucose stimulation. Further study demonstrated that a low concentration of extracellular bicarbonate significantly impaired the functioning of pancreatic β cells by reducing coupling Ca |
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