Suckale Jakob, Solimena Michele
Experimental Diabetology, School of Medicine, Dresden University of Technology, Dresden, Germany.
Front Biosci. 2008 May 1;13:7156-71. doi: 10.2741/3218.
The Islets of Langerhans form a nutrient sensing network spread throughout the pancreas. They are tightly connected to the source organ, the intestine, and the target organs--liver, muscle, and fat cells. The expression of a unique set of proteins enables beta cells, the most frequent islet cell type, to detect elevated blood glucose levels and secrete insulin accordingly. Clustered beta-cells achieve tighter regulation of glucose-induced insulin secretion by coordination through cell surface proteins. They also adjust their secretory capacity and flow to avoid being damaged. The immediate reaction of the beta cell to nutrients is regulated by translational mechanisms, while longer term adaptations involve changes in transcription. Glucose increases overall protein synthesis in beta-cells but selectively boosts translation of some secretory proteins including insulin. This may be mediated through recognition of RNA motifs in the untranslated regions of those messengers. If essential molecular components of this nutrient sensing system are broken or fail due to repeated stress, beta cells malfunction, which on a larger scale manifest as diseases like diabetes mellitus.
朗格汉斯胰岛形成了一个遍布整个胰腺的营养感知网络。它们与源器官肠道以及靶器官——肝脏、肌肉和脂肪细胞紧密相连。一组独特蛋白质的表达使胰岛中最常见的细胞类型β细胞能够检测出血糖水平升高,并相应地分泌胰岛素。聚集的β细胞通过细胞表面蛋白的协调作用实现对葡萄糖诱导的胰岛素分泌更严格的调控。它们还会调整自身的分泌能力和流量以避免受损。β细胞对营养物质的即时反应受翻译机制调控,而长期适应则涉及转录变化。葡萄糖会增加β细胞中的整体蛋白质合成,但会选择性地促进包括胰岛素在内的一些分泌蛋白的翻译。这可能是通过识别这些信使RNA非翻译区中的RNA基序来介导的。如果这个营养感知系统的关键分子成分因反复应激而受损或失效,β细胞就会发生功能障碍,在更大范围内表现为糖尿病等疾病。