Islet-specific microRNA changes driven by nutrient shift trigger postnatal beta-cell maturation - intact islet microRNAs

We found that in rodents, postnatal beta-cell maturation is associated with changes in the expression of several islet microRNAs and discovered that these modifications are driven by changes in the nutrient supply. Mimicking the microRNA changes observed during ß-cell maturation in newborn rat islet cells was sufficient to promote glucose-induced insulin release and to achieve a mature ß-cell secretory phenotype. Moreover, the modifications in the level of some of these microRNAs reduced the proliferation of newborn ß-cells, suggesting that they contribute to the limited proliferative capacity of adult ß-cells. These findings demonstrated that miRNAs contribute to postnatal beta-cell maturation and development. Their role is likely to promote beta-cell adaptation to fule supply and to maintain glucose homeostasis by regulating insulin release and proliferation.我们在啮齿类动物中发现，出生后胰岛β细胞的成熟过程与多种胰岛微小RNA（microRNA）的表达变化存在显著关联，同时证实此类表达修饰的发生由营养供给的改变所驱动。模拟新生大鼠胰岛细胞在β细胞成熟过程中观察到的微小RNA表达变化，即可有效促进葡萄糖诱导的胰岛素分泌，并使细胞获得成熟的β细胞分泌表型。此外，部分这类微小RNA的水平变化会抑制新生β细胞的增殖，这表明这些微小RNA参与调控成年β细胞有限的增殖能力。本研究结果证实，微小RNA参与出生后β细胞的成熟与发育过程。它们的作用可能是通过调控胰岛素分泌与细胞增殖，促进β细胞对营养供给的适应性，并维持葡萄糖稳态。