谷氨酸的促胰岛素分泌作用依赖于对MIN 6 β细胞中ATP敏感性钾通道活性的抑制。

Insulinotropic action of glutamate is dependent on the inhibition of ATP-sensitive potassium channel activities in MIN 6 beta cells.

作者信息

Katsuta Hidenori, Ozawa Sachihiko, Ninomiya Tomonori, Shimoyama Tatsuhiro, Ito Eisuke, Tanaka Toshiaki, Yamaguchi Shinya, Katahira Hiroshi, Nagamatsu Shinya, Horie Minoru, Ishida Hitoshi

机构信息

Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.

出版信息

Biochem Biophys Res Commun. 2003 Nov 21;311(3):660-4. doi: 10.1016/j.bbrc.2003.10.043.

DOI:10.1016/j.bbrc.2003.10.043

PMID:14623322

Abstract

To investigate the cellular mechanism of insulinotropic effect of glutamate in pancreatic beta cells, we utilized patch-clamp technique to monitor directly the activities of ATP-sensitive potassium channels (K(ATP) channels). Dimethylglutamate (5mM), a membrane-permeable analog of glutamate, augmented the insulin release induced by the stimulatory concentrations of glucose (p<0.05-0.01). In the cell-attached configurations, dimethylglutamate reversibly and significantly suppressed the K(ATP) channel activities (p<0.01). On the other hand, no significant effect was observed when glutamate itself was applied to the inside-out patches, whereas the prompt and reversible suppression was recorded in the case of ATP (p<0.01). These results indicate that the insulinotropic action of glutamate in beta cells could be derived from the inhibition of K(ATP) channel activities, probably due to generation of messengers via intracellular metabolism such as ATP.

摘要

为了研究谷氨酸在胰腺β细胞中促胰岛素分泌作用的细胞机制，我们利用膜片钳技术直接监测ATP敏感性钾通道（K(ATP)通道）的活性。二甲基谷氨酸（5mM），一种谷氨酸的膜通透性类似物，增强了刺激浓度葡萄糖诱导的胰岛素释放（p<0.05 - 0.01）。在细胞贴附模式下，二甲基谷氨酸可逆且显著地抑制K(ATP)通道活性（p<0.01）。另一方面，当将谷氨酸本身应用于内面向外的膜片时未观察到显著影响，而在ATP的情况下记录到迅速且可逆的抑制（p<0.01）。这些结果表明，谷氨酸在β细胞中的促胰岛素分泌作用可能源于对K(ATP)通道活性的抑制，这可能是由于通过细胞内代谢如ATP产生信使所致。