NKCC transport mediates the insulinotropic effects of taurine and other small neutral amino acids

Aims: Despite its high concentration in pancreatic islets of Langerhans and broad range of antihyperglycemic effects, the route facilitating the import of dietary taurine into pancreatic β-cell and mechanisms underlying its insulinotropic activity are unclear. We therefore studied the impact of taurine on beta-cell function, alongside that of other small neutral amino acids, L-alanine and L-proline. Main methods: Pharmacological profiling of insulin secretion was conducted using clonal BRIN BD11 β-cells, the impact of taurine on the metabolic fate of glucose carbons was assessed using NMR and the findings were verified by real-time imaging of Ca²⁺ dynamics in the cytosol of primary mouse and human islet beta-cells. Key findings: In our hands, taurine, alanine and proline induced secretory responses that were dependent on the plasma membrane depolarisation, import of Ca²⁺, homeostasis of K⁺ and Na⁺ as well as on cell glycolytic and oxidative metabolism. Taurine shifted the balance between the oxidation and anaplerosis towards the latter, in BRIN BD11 beta-cells. Furthermore, the amino acid signalling was significantly attenuated by inhibition of Na⁺-K⁺-Cl⁻ symporter (NKCC). Significance: These data suggest that taurine, like L-alanine and L-proline, acutely induces glucose-dependent insulin-secretory responses by modulating electrogenic Na⁺ transport, with potential role of intracellular K⁺ and Cl⁻ in the signal transduction. The acute action delineated would be consistent with antidiabetic potential of dietary taurine supplementation.