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

• Published in: Life sciences (1973) 2023-03, Vol.316, p.121402-121402, Article 121402
• Main Authors: Turbitt, Julie, Brennan, Lorraine, Moffett, R. Charlotte, Flatt, Peter R., Johnson, Paul R.V., Tarasov, Andrei I., McClenaghan, Neville H.
• Format: Article
• Language: English
• Subjects: Alanine - metabolism; Alanine - pharmacology; Amino acids; Amino Acids, Neutral - metabolism; Amino Acids, Neutral - pharmacology; Animals; Ca2+ dynamics; Cell Line; Glucose - metabolism; Humans; Hypoglycemic Agents - pharmacology; Insulin - metabolism; Insulin secretion; Islets of Langerhans - metabolism; Mice; Na+-K+-Cl− transporter; Oxidative metabolism; Proline - metabolism; Taurine; Taurine - metabolism; Taurine - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121402

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 Ca2+ 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 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). 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. •Taurine elevates cytosolic Ca2+ to induce insulin release from pancreatic β-cells.•The insulinotropic effect of taurine depends on oxidative metabolism, K+ and Na+ homeostasis.•Na+-K+-Cl− symporter has a key role in transport of taurine and small neutral amino acids into the β-cell.•Taurine regulates the balance between oxidative metabolism and anaplerosis in β-cells.