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

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. 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 Ca dynamics in the cytosol of primary mouse and human islet beta-cells. In our hands, taurine, alanine and proline induced secretory responses that were dependent on the plasma membrane depolarisation, import of Ca , 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). 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. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.]