From the *Department of Clinical Science and Education, Karolinska Institutet, South Hospital, Stockholm, Sweden; †Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden; and ‡Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden.
Pancreas. 2014 May;43(4):597-604. doi: 10.1097/MPA.0000000000000027.
Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca(2+)-activated monovalent cation channel, is involved in the stimulus-secretion coupling in the mouse pancreatic β-cells. We have studied the role of the TRPM5 channel in regulating insulin secretion and cytoplasmic free Ca(2+) concentration (Ca(2+)) in the rat β-cells by using triphenylphosphine oxide, a selective inhibitor of the channel.
Insulin secretion from islets from Sprague-Dawley rats was measured in batch incubations. Cytoplasmic free Ca(2+) concentration was measured from single β-cells by fura-2-based microfluorometry.
Triphenylphosphine oxide did not alter insulin secretion and Ca(2+) response triggered by KCl or fructose. It inhibited insulin secretion in response to glucose, L-arginine, and glucagon-like peptide 1. It also inhibited glucose-induced insulin secretion by mechanisms that are independent of the adenosine triphosphate-sensitive potassium channels and Ca(2+) increase.
Our results suggest that in the rat islets, TRPM5 is involved in mediating insulin secretion by glucose and l-arginine and in potentiating the glucose-induced insulin secretion by glucagon-like peptide 1.
几项研究报告称，瞬时受体电位 melastatin 样亚型 5（TRPM5）通道是一种 Ca（2+）激活的单价阳离子通道，参与了小鼠胰腺β细胞中的刺激-分泌偶联。我们通过使用三苯基氧化膦（TRPM5 通道的选择性抑制剂）研究了 TRPM5 通道在调节大鼠β细胞胰岛素分泌和细胞质游离 Ca（2+）浓度([Ca（2+）]（i））中的作用。
在分批孵育中测量 Sprague-Dawley 大鼠胰岛的胰岛素分泌。通过基于 fura-2 的微荧光法从单个β细胞测量细胞质游离 Ca（2+）浓度。
三苯基氧化膦不改变 KCl 或果糖触发的胰岛素分泌和[Ca（2+）]（i）反应。它抑制葡萄糖、L-精氨酸和胰高血糖素样肽 1 引起的胰岛素分泌。它还通过独立于三磷酸腺苷敏感钾通道和[Ca（2+）]（i）增加的机制抑制葡萄糖诱导的胰岛素分泌。
我们的结果表明，在大鼠胰岛中，TRPM5 参与介导葡萄糖和 L-精氨酸引起的胰岛素分泌，并增强胰高血糖素样肽 1 引起的葡萄糖诱导的胰岛素分泌。
