Ernst Sara J, Aguilar-Bryan Lydia, Noebels Jeffrey L
Departments of Molecular and Human Genetics, Developmental Neurogenetics Laboratory, Baylor College of Medicine, Houston, Texas 77030, USA.
Endocrinology. 2009 Mar;150(3):1132-9. doi: 10.1210/en.2008-0991. Epub 2008 Nov 6.
Glucose-stimulated insulin and glucagon release regulates glucose homeostasis by an excitation-secretion coupling pathway beginning with ATP-sensitive K(+) channel closure, membrane depolarization, and entry of calcium ions to stimulate exocytosis. The contribution of voltage-gated sodium channels to this release pathway is still being elucidated. We demonstrate that loss of Scn1b, a major regulatory subunit expressed with Na(v)1.7 protein in mouse pancreatic islets, reduces glucose-stimulated insulin and glucagon secretion in vitro and in vivo, resulting in severe fed and fasting hypoglycemia. This genetic mouse model is the first to demonstrate that sodium channelopathy impairs the physiological excitation-release coupling pathway for pancreatic insulin and glucagon release.
葡萄糖刺激的胰岛素和胰高血糖素释放通过一种兴奋-分泌偶联途径调节葡萄糖稳态，该途径始于ATP敏感性钾通道关闭、膜去极化以及钙离子内流以刺激胞吐作用。电压门控钠通道对这一释放途径的作用仍在阐明之中。我们证明，Scn1b是在小鼠胰岛中与Na(v)1.7蛋白共同表达的主要调节亚基，其缺失会在体外和体内降低葡萄糖刺激的胰岛素和胰高血糖素分泌，导致严重的进食后和空腹低血糖。这个基因小鼠模型首次证明，钠通道病会损害胰腺胰岛素和胰高血糖素释放的生理兴奋-释放偶联途径。
