哺乳动物D-氨酸控制胰腺中的胰岛素分泌
Robin Roychaudhuri1, Timothy West2, Soumyaroop Bhattacharya3
1Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Birth Defects, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Molecular metabolism
|October 5, 2024
概括
内源性D-氨酸是哺乳动物胰腺中新发现的分子,它调节胰岛素分泌. 研究表明它在糖尿病模型中的作用,以及它通过血清蛋白赛马酶 (SR) 的合成.
科学领域:
- 生物化学 生物化学
- 内分泌学 在内分泌学.
- 代谢过程中的代谢.
背景情况:
- D-氨基酸越来越多地被认为是它们在哺乳动物中的功能作用.
- 这项研究报告了哺乳动物胰腺内内源性D-氨酸的首次鉴定.
研究的目的:
- 在哺乳动物胰腺中识别和表征内源性D-氨酸.
- 阐明D-氨酸在胰岛素分泌中的功能作用及其在糖尿病中的参与.
主要方法:
- 使用了一种新的立体特异生物发光试验,性染色学和酶动力学.
- 采用了转基因小鼠模型 (SR-/-),STZ和NOD糖尿病模型,以及用于功能分析的分离小鼠/人群岛.
- 在各种实验系统中研究葡萄糖刺激胰岛素分泌 (GSIS).
主要成果:
- D-氨酸是由血清酶 (SR) 合成的;SR-/-小鼠表现出显著更高的胰岛素水平,肝糖原和体.
- 在SR-/-小鼠中,多余的胰岛素被存储为粉样蛋白.
- D-氨酸在孤立的小岛和细胞系中表现出强大的胰岛素分泌抑制,超过了D-氨酸.
- 糖尿病状态 (STZ,NOD) 显示胰腺中D-氨酸和SR表达增加.
- SR缺乏影响了cAMP水平,DNA甲基转移酶活性,CREB酸化和Ins1促进剂甲基化.
- D-氨酸代谢涉及D-氨基酸氧化酶和通过ASCT2和Asc1.
- 食甲基供体在SR-/-小鼠中部分恢复胰岛素水平和DNMT活性.
结论:
- 内源性D-氨酸是由哺乳动物胰腺中的血清酶酶合成的.
- D-氨酸作为胰岛素分泌的关键调节剂.
- D-氨酸代谢和信号的失调与糖尿病疾病有关.
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