In pancreatic beta cells, the entry of glucose and downstream signaling for insulin release is regulated by the glucose transporter 2 (Glut2) in rodents. Dysfunction of the insulin-signaling cascade may lead to diabetes mellitus. Gangliosides, sialic acid-containing glycosphingolipids (GSLs), have been reported to modulate the function of several membrane proteins.Murine islets express predominantly sialylated GSLs, particularly the simple gangliosides GM3 and GD3 having a potential modulatory role in Glut2 activity. Conditional, tamoxifen-inducible gene targeting in pancreatic islets has now shown that mice lacking the glucosylceramide synthase (Ugcg), which represents the rate-limiting enzyme in GSL biosynthesis, displayed impaired glucose uptake and showed reduced insulin secretion. Consequently, mice with pancreatic GSL deficiency had higher blood glucose levels than respective controls after intraperitoneal glucose application. High-fat diet feeding enhanced this effect. GSL-deficient islets did not show apoptosis or ER stress and displayed a normal ultrastructure. Their insulin content, size and number were similar as in control islets. Isolated beta cells from GM3 synthase null mice unable to synthesize GM3 and GD3 also showed lower glucose uptake than respective control cells, corroborating the results obtained from the cell-specific model. We conclude that in particular the negatively charged gangliosides GM3 and GD3 of beta cells positively influence Glut2 function to adequately respond to high glucose loads.

中文翻译：

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神经节苷脂调节葡萄糖应激下胰腺β细胞的胰岛素分泌。

在胰腺 β 细胞中，葡萄糖的进入和胰岛素释放的下游信号受啮齿动物中的葡萄糖转运蛋白 2 (Glut2) 调节。胰岛素信号级联的功能障碍可能导致糖尿病。据报道，神经节苷脂、含唾液酸的鞘糖脂 (GSL) 可调节几种膜蛋白的功能。鼠胰岛主要表达唾液酸化的 GSL，特别是简单的神经节苷脂 GM3 和 GD3，在 Glut2 活性中具有潜在的调节作用。胰岛中的条件性他莫昔芬诱导基因靶向现已表明缺乏葡萄糖神经酰胺合酶 ( Ugcg) 的小鼠)，代表 GSL 生物合成中的限速酶，显示葡萄糖摄取受损和胰岛素分泌减少。因此，在腹腔注射葡萄糖后，胰腺 GSL 缺乏小鼠的血糖水平高于相应的对照组。高脂肪饮食喂养增强了这种效果。GSL 缺陷的胰岛没有显示细胞凋亡或内质网应激，并显示出正常的超微结构。它们的胰岛素含量、大小和数量与对照胰岛相似。从无法合成 GM3 和 GD3 的 GM3 合酶无效小鼠中分离出的 β 细胞也显示出比各自的对照细胞更低的葡萄糖摄取，这证实了从细胞特异性模型中获得的结果。