School of Biomedical Sciences, Ulster University, Coleraine, UK.
UCD Institute of Food and Health, UCD School of Agriculture and Food Science, University College Dublin, Dublin 4, Republic of Ireland.
Acta Physiol (Oxf). 2024 Mar;240(3):e14101. doi: 10.1111/apha.14101. Epub 2024 Jan 20.
Despite 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.
The 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.
Taurine 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 Ca 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 K channel inhibitors sensitized or, respectively, desensitized β-cells to the acute taurine stimulus.
Together, 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.
尽管牛磺酸在胰岛 Langerhans 中含量丰富，且已证实具有抗高血糖作用，但人们尚未充分考虑这种必需氨基酸对胰岛 β 细胞生物学的影响，这促使我们开展了目前的研究，以探究牛磺酸进入 β 细胞的分子选择性及其在急性和慢性细胞内的相互作用。
通过用一系列氨基酸类似物（在 2-20mM 下进行检测）处理克隆胰腺 BRIN BD11 β 细胞和原代小鼠及人胰岛，探测牛磺酸转运的分子方面，使用激素释放和细胞内信号成像作为替代检测指标。利用已知的分泌调节剂来分析牛磺酸与急性和慢性细胞内信号的相互作用。
牛磺酸转运体 TauT 在胰岛 β 细胞中表达，牛磺酸及其类似物的转运具有较弱的磺酸盐特异性，但对转运体的分子量具有显著的敏感性。牛磺酸、次牛磺酸、同型牛磺酸和 β-丙氨酸以葡萄糖依赖性方式增强胰岛素分泌，该作用可被胞质 Ca 和 cAMP 增强。牛磺酸对胰岛的急性和慢性胰岛素促分泌作用对 GLP-1、福司可林、甲苯磺丁脲和膜去极化的协同作用高度敏感，而对 PKC 和 CCK8 受体的激活不敏感。用 GLP-1 或 K 通道抑制剂预培养可使 β 细胞对急性牛磺酸刺激产生敏感性或脱敏。
这些数据共同证明了牛磺酸在胰岛素分泌和 β 细胞功能方面发挥一系列有益作用的途径，这与其膳食低剂量补充的抗糖尿病潜力一致。
