Affiliation:
1. School of Biomedical Sciences Ulster University Coleraine UK
2. UCD Institute of Food and Health, UCD School of Agriculture and Food Science University College Dublin Dublin 4 Republic of Ireland
3. UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin Dublin 4 Republic of Ireland
4. Nuffield Department of Surgical Sciences, Oxford Centre for Diabetes, Endocrinology and Metabolism University of Oxford, Churchill Hospital Oxford UK
5. Oxford Biomedical Research Centre (OxBRC) Oxford UK
6. Department of Life Sciences Atlantic Technological University Sligo Republic of Ireland
Abstract
AbstractAimDespite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet β‐cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into β‐cells and its acute and chronic intracellular interactions.MethodsThe molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 β‐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.ResultsTaurine transporter TauT was expressed in the islet β‐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 β‐alanine enhanced insulin secretion in a glucose‐dependent manner, an action potentiated by cytosolic Ca2+ and cAMP. Acute and chronic β‐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 KATP channel inhibitors sensitized or, respectively, desensitized β‐cells to the acute taurine stimulus.ConclusionTogether, these data demonstrate the pathways whereby taurine exhibits a range of beneficial effects on insulin secretion and β‐cell function, consistent with the antidiabetic potential of its dietary low‐dose supplementation.