Relations between Glucose and d-Amino Acids in the Modulation of Biochemical and Functional Properties of Rodent Islets of Langerhans.
Relations between Glucose and d-Amino Acids in the Modulation of Biochemical and Functional Properties of Rodent Islets of Langerhans.
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DOI：
10.1021/acsomega.3c05983
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发表时间：
2023-12-19
期刊：
影响因子：
4.1
通讯作者：
Sweedler, Jonathan V.
中科院分区：
文献类型：
--
作者：
Lee, Cindy J.;Lee, Dong-Kyu;Wei, I-An;Qiu, Tian A.;Rubakhin, Stanislav S.;Roper, Michael G.;Sweedler, Jonathan V.
d-氨基酸（d-AAs）在哺乳动物内分泌系统（特别是胰岛）中的细胞间信号传导作用因其可能参与调节葡萄糖代谢而引起越来越多的关注。先前的研究发现丝氨酸消旋酶[产生d-丝氨酸（d-Ser）]和d-丙氨酸（d-Ala）在胰岛素分泌β细胞内以及d-天冬氨酸（d-Asp）在胰高血糖素分泌α细胞内共定位。在胰岛中表达的功能性N-甲基-d-天冬氨酸受体参与葡萄糖刺激的胰岛素分泌的调节，并具有几个d-AA的结合位点。然而，在葡萄糖刺激期间胰岛中d-AA水平的调节以及胰岛对不同水平的细胞外d-AA的响应的知识是有限的。在这项研究中，我们确定了细胞内和细胞外水平的d-Ser，d-Ala，和d-Asp的文化孤立的啮齿类动物胰岛暴露于不同水平的细胞外葡萄糖。我们发现，对映体的细胞内水平表现出很大的变异性，并在一般情况下，不受细胞外葡萄糖水平。然而，与使用3 mM葡萄糖的对照条件相比，在补充有20 mM浓度的葡萄糖的胰岛培养基中观察到显著较低水平的细胞外d-Ser和d-Ala。葡萄糖诱导的细胞内游离钙浓度（[Ca 2 +]i）的振荡，胰岛素分泌的代理，调制的外源性应用的d-Ser和d-Ala，但不是由他们的l-立体异构体。我们的研究结果提供了新的见解d-AAs在胰岛的生物化学和功能的作用。
The cell-to-cell signaling role of d-amino acids (d-AAs) in the mammalian endocrine system, particularly in the islets of Langerhans, has drawn growing interest for their potential involvement in modulating glucose metabolism. Previous studies found colocalization of serine racemase [produces d-serine (d-Ser)] and d-alanine (d-Ala) within insulin-secreting beta cells and d-aspartate (d-Asp) within glucagon-secreting alpha cells. Expressed in the islets, functional N-methyl-d-aspartate receptors are involved in the modulation of glucose-stimulated insulin secretion and have binding sites for several d-AAs. However, knowledge of the regulation of d-AA levels in the islets during glucose stimulation as well as the response of islets to different levels of extracellular d-AAs is limited. In this study, we determined the intracellular and extracellular levels of d-Ser, d-Ala, and d-Asp in cultures of isolated rodent islets exposed to different levels of extracellular glucose. We found that the intracellular levels of the enantiomers demonstrated large variability and, in general, were not affected by extracellular glucose levels. However, significantly lower levels of extracellular d-Ser and d-Ala were observed in the islet media supplemented with 20 mM concentration of glucose compared to the control condition utilizing 3 mM glucose. Glucose-induced oscillations of intracellular free calcium concentration ([Ca2+]i), a proxy for insulin secretion, were modulated by the exogenous application of d-Ser and d-Ala but not by their l-stereoisomers. Our results provide new insights into the roles of d-AAs in the biochemistry and function of pancreatic islets.
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