（封面图片：作者建立的胰高血糖素调节模型，背景中的胰岛α细胞（红色）表达囊泡谷氨酸转运体（绿色），而β细胞分泌胰岛素（蓝色）。图片提供：Nathan Bress）
生物谷报道：美国和瑞典科学家联合在《细胞—代谢》（Cell Metabolism）上发表封面文章，证实人类胰岛α细胞能表达一种对于胰高血糖素的释放非常关键的促离子型谷氨酸受体（ionotropic glutamate receptor iGluRs）。
血糖稳态（glucose homeostasis）的一个重要特征是胰岛α细胞有效的释放胰高血糖素（glucagon），胰高血糖素又被称为抗胰岛素或是胰岛素B。人类胰高血糖素是以N-末端组氨酸为起点，C-末端苏氨酸为终点的29个氨基酸组成的一条单链肽，分子量为3485。其主要作用是对抗胰岛素，起着使血糖增加的作用。然而目前，科学家对于调节胰高血糖素分泌过程的分子学机制还知之甚少。
实验中，研究人员分析了谷氨酸盐（glutamate）作为正向自分泌信号在人类、猴子、小鼠胰岛的胰高血糖素释放过程中的作用。结果发现，谷氨酸盐的正反馈极大的促进了胰高血糖素的分泌，而一旦血糖浓度上升，胰高血糖素的分泌就会受到胰岛素以及锌离子或是γ-氨基丁酸（GABA）的限制。
血糖浓度的下降能促使胰岛α细胞释放谷氨酸盐。谷氨酸盐接着作用于AMPA和kainate型的促离子型谷氨酸受体，并使得细胞膜去极化，钙离子通道被打开，最终使得细胞质中的自由钙离子浓度增加，从而促进胰高血糖素的释放。在小鼠的活体实验中，阻碍促离子型谷氨酸受体将会降低胰高血糖素的释放，并加剧胰岛素导致的血糖过低症状。因此，谷氨酸盐的自分泌反馈环路使得胰岛α细胞具有了有效加强自身分泌活性的能力，这是在任何生理条件下保证充足的胰高血糖素释放不可或缺的先决条件。（生物谷www.bioon.com）
生物谷推荐原始出处：
Cell Metabolism，Vol 7, 545-554, 04 June 2008，Over Cabrera, Per-Olof Berggren
Glutamate Is a Positive Autocrine Signal for Glucagon Release
Over Cabrera,1,2 M. Caroline Jacques-Silva,1 Stephan Speier,2 Shao-Nian Yang,2 Martin Köhler,2 Alberto Fachado,1 Elaine Vieira,3 Juleen R. Zierath,3 Richard Kibbey,4 Dora M. Berman,1 Norma S. Kenyon,1 Camillo Ricordi,1 Alejandro Caicedo,1, and Per-Olof Berggren1,2,
1 Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
2 The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
3 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden
4 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
Corresponding author
Alejandro Caicedo
acaicedo@med.miami.edu
Corresponding author
Per-Olof Berggren
per-olof.berggren@ki.se
Summary
An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic α cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human α cells express ionotropic glutamate receptors (iGluRs) that are essential for glucagon release. A lowering in glucose concentration results in the release of glutamate from the α cell. Glutamate then acts on iGluRs of the AMPA/kainate type, resulting in membrane depolarization, opening of voltage-gated Ca2+ channels, increase in cytoplasmic free Ca2+ concentration, and enhanced glucagon release. In vivo blockade of iGluRs reduces glucagon secretion and exacerbates insulin-induced hypoglycemia in mice. Hence, the glutamate autocrine feedback loop endows the α cell with the ability to effectively potentiate its own secretory activity. This is a prerequisite to guarantee adequate glucagon release despite relatively modest changes in blood glucose concentration under physiological conditions.
