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

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

Synthalin::a lost lesson for glucagon suppression in diabetes therapeutics

Objectives Within mammalian pancreatic islets, there are two major endocrine cell types, beta-cells which secrete insulin and alpha-cells which secrete glucagon. Whereas, insulin acts to lower circulating glucose, glucagon counters this by increasing circulating glucose via the mobilisation of glycogen. Synthalin A (Syn A) was the subject of much research in the 1920s and 1930s as a potential pancreatic alpha-cell toxin to block glucagon secretion. However, with the discovery of insulin and its lifesaving use in patients with diabetes, research on Syn-A was discontinued. Key findings This short review looks back on early studies performed with Syn A in animals and humans with diabetes. These are relevant today because both type 1 and type 2 diabetes are now recognised as states of not only insulin deficiency but also glucagon excess. Summary Lessons learned from this largely forgotten portfolio of work and therapeutic strategy aimed at limiting the number or function of islet alpha-cells might be worthy of reconsideration