Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic α-cells
Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic α-cells
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DOI：
10.2337/diabetes.54.6.1789
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发表时间：
2005-06-01
期刊：
影响因子：
7.7
通讯作者：
Rutter, GA
中科院分区：
文献类型：
--
作者：
Ravier, MA;Rutter, GA
低血糖刺激胰高血糖素释放的机制仍然知之甚少。特别是，β细胞分泌产物的直接代谢偶联与旁分泌调节的相对重要性尚未得到解决。在这里，我们比较了1）完整小鼠胰岛内的α细胞，2）解离的α细胞和3）克隆α TC 1 -9细胞对葡萄糖的反应。ATP（[ATP]（c））或Ca 2+（[Ca 2 +]（c））的游离胞质浓度分别使用α-细胞靶向的萤火虫荧光素酶或基于绿色荧光蛋白的Ca 2+探针（“pericam”）成像。与葡萄糖对α细胞氧化代谢的直接影响一致，葡萄糖浓度增加（从0或3 mmol/l至20 mmol/l）使完整胰岛内α细胞中的[ATP]增加7-9%，在aTC 1 -9细胞中增加4%。此外，葡萄糖还剂量依赖性地降低游离α细胞和α TC 1 -9细胞中[Ca 2 +]振荡的频率。虽然葡萄糖的作用被外源性胰岛素模仿，但当用渥曼青霉素阻断胰岛素信号时，它们被保留下来。ZnCl 2的添加略微增加了[Ca 2 +]振荡的频率，但在大多数条件下未能影响胰岛或α TC 1 -9细胞的胰高血糖素释放。我们得出结论，葡萄糖和胰岛素，但不是锌离子，独立抑制胰高血糖素分泌的小鼠。
The mechanisms by which hypoglycemia stimulates glucagon release are still poorly understood. In particular, the relative importance of direct metabolic coupling versus paracrine regulation by beta-cell secretory products is unresolved. Here, we compare the responses to glucose of 1) alpha-cells within the intact mouse islet, 2) dissociated a-cells, and 3) clonal alpha TC1-9 cells. Free cytosolic concentrations of ATP ([ATP](c)) or Ca2+ ([Ca2+](c)) were imaged using a-cell-targeted firefly luciferase or a green fluorescent protein-based Ca2+ probe ("pericam"), respectively. Consistent with a direct effect of glucose on alpha-cell oxidative metabolism, an increase in glucose concentration (from 0 or 3 mmol/l to 20 mmol/l) increased [ATP], by 7-9% in alpha-cells within the intact islet and by similar to 4% in aTC1-9 cells. Moreover, glucose also dose-dependently decreased the frequency of [Ca2+], oscillations in both dissociated alpha-cells and alpha TC1-9 cells. Although the effects of glucose were mimicked by exogenous insulin, they were preserved when insulin signaling was blocked with wortmannin. Addition of ZnCl2 slightly increased the frequency of [Ca2+], oscillations but failed to affect glucagon release from either islets or alpha TC1-9 cells under most conditions. We conclude that glucose and insulin, but not Zn2+ ions, independently suppress glucagon secretion in the mouse.