Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor
Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor
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DOI：
10.1126/science.aaf8430
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发表时间：
2016-09-30
期刊：
影响因子：
56.9
通讯作者：
Leopold, Pierre
中科院分区：
文献类型：
--
作者：
Delanoue, Renald;Meschi, Eleonora;Leopold, Pierre
动物通过胰岛素-胰岛素样生长因子信号传导的一般调节来调整其生长速度和体型以适应可用的营养物质。在果蝇中，膳食氨基酸促进脑胰岛素样肽（Dilps）在血淋巴中的释放，进而激活全身器官的生长。胰岛素产生细胞的 Dilp 分泌涉及通过脂肪细胞产生的未知细胞因子的中继。在这里，我们将 Methuselah (Mth) 确定为胰岛素生成细胞中适当的营养耦合所需的促胰液素-肠促胰岛素受体亚家族成员。我们通过遗传和离体器官培养实验进一步表明，Mth 配体 Stunted (Sun) 是一种由脂肪细胞产生的循环促胰岛素肽。因此，Sun 和 Mth 定义了一种新的跨器官回路，可以根据营养物质调节生理胰岛素水平。
Animals adapt their growth rate and body size to available nutrients by a general modulation of insulin-insulin-like growth factor signaling. In Drosophila, dietary amino acids promote the release in the hemolymph of brain insulin-like peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by insulin-producing cells involves a relay through unknown cytokines produced by fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor subfamily member required in the insulin-producing cells for proper nutrient coupling. We further show, using genetic and ex vivo organ culture experiments, that the Mth ligand Stunted (Sun) is a circulating insulinotropic peptide produced by fat cells. Therefore, Sun and Mth define a new cross-organ circuitry that modulates physiological insulin levels in response to nutrients.