Incretins are gut peptides that are secreted by enteroendocrine cells (EECs) in response to food to stimulate a decrease in blood glucose levels. In mammals, incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) stimulate the secretion of insulin by acting on pancreatic β-cells. EECs in the Drosophila gut also produce incretins, including neuropeptide F (NPF), which can stimulate insulin secretion from brain neurosecretory cells. In a new study, Chen and colleagues reveal that NPF also regulates Drosophila aging, notably by acting on insulin signaling. The team showed that suppressing the secretion of NPF by EECs or the expression of NPF receptors by insulin-producing neurons extended female Drosophila longevity. They also showed that the NPF–insulin axis was regulating aging by controlling juvenile hormone production by the corpora allata, an endocrine gland located behind the brain. Altogether, these findings indicate that gut-derived incretins can modulate Drosophila aging through a gut–brain–corpora allata axis. Given the increasing use of incretin-mimetic drugs to treat diabetes and obesity, the effects of incretin analogs on human aging should be further investigated.

Original reference: Chen, J. et al. Proc. Natl Acad. Sci. USA 121, e2411987121 (2024)

肠促胰岛素是肠内分泌细胞 （EEC） 响应食物分泌的肠道肽，以刺激血糖水平降低。在哺乳动物中，胰高血糖素样肽 1 （GLP-1） 和葡萄糖依赖性促胰岛素肽 （GIP） 等肠促胰岛素通过作用于胰腺β细胞来刺激胰岛素的分泌。果蝇肠道中的 EEC 还产生肠促胰岛素，包括神经肽 F （NPF），它可以刺激大脑神经分泌细胞分泌胰岛素。在一项新的研究中，Chen 及其同事揭示了 NPF 还调节果蝇的衰老，特别是通过作用于胰岛素信号传导。该团队表明，抑制 EEC 分泌 NPF 或产生胰岛素的神经元表达 NPF 受体可延长女性果蝇的寿命。他们还表明，NPF-胰岛素轴通过控制位于大脑后面的内分泌腺 allata 产生的幼年激素来调节衰老。总而言之，这些发现表明肠道来源的肠促胰岛素可以通过肠道-大脑-体 allata 轴调节果蝇衰老。鉴于越来越多地使用肠促胰岛素模拟药物来治疗糖尿病和肥胖症，应进一步研究肠促胰岛素类似物对人类衰老的影响。

原始参考资料：Chen， J. et al. Proc. Natl Acad. Sci. USA121， e2411987121 （2024）