Molecular determinants and intracellular targets of taurine signalling in pancreatic islet -cells

Aim: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet beta-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into beta-cells and its acute and chronic intracellular interactions.Methods: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 beta-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals.Results: Taurine transporter TauT was expressed in the islet beta-cells, with the transport of taurine and homologs having a weak sulfonate specificity but significant sensitivity to the molecular weight of the transporter. Taurine, hypotaurine, homotaurine, and beta-alanine enhanced insulin secretion in a glucose-dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic beta-cell insulinotropic effects of taurine were highly sensitive to co-agonism with GLP-1, forskolin, tolbutamide, and membrane depolarization, with an unanticipated indifference to the activation of PKC and CCK8 receptors. Pre-culturing with GLP-1 or K-ATP channel inhibitors sensitized or, respectively, desensitized beta-cells to the acute taurine stimulus.Conclusion: Together, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and beta-cell function, consistent with the antidiabetic potential of its dietary low-dose supplementation.