Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
Diabetes Center of the Faculty of Medicine, University of Geneva, Geneva, Switzerland.
J Endocrinol. 2023 Jul 11;258(2). doi: 10.1530/JOE-22-0304. Print 2023 Aug 1.
Cell protein biosynthesis is regulated by different factors, but implication of intercellular contacts on alpha and beta cell protein biosyntheses activity has not been yet investigated. Islet cell biosynthetic activity is essential in regulating not only the hormonal reserve within cells but also in renewing all the proteins involved in the control of secretion. Here we aimed to assess whether intercellular interactions affected similarly secretion and protein biosynthesis of rat alpha and beta cells. Insulin and glucagon secretion were analyzed by ELISA or reverse hemolytic plaque assay, and protein biosynthesis evaluated at single cell level using bioorthogonal noncanonical amino acid tagging. Regarding beta cells, we showed a positive correlation between insulin secretion and protein biosynthesis. We also observed that homologous contacts increased both activities at low or moderate glucose concentrations. By contrast, at high glucose concentration, homologous contacts increased insulin secretion and not protein biosynthesis. In addition, heterogeneous contacts between beta and alpha cells had no impact on insulin secretion and protein biosynthesis. Regarding alpha cells, we showed that when they were in contact with beta cells, they increased their glucagon secretion in response to a drop of glucose concentration, but, on the other hand, they decreased their protein biosynthesis under any glucose concentrations. Altogether, these results emphasize the role of intercellular contacts on the function of islet cells, showing that intercellular contacts increased protein biosynthesis in beta cells, except at high glucose, and decreased protein biosynthesis in alpha cells even when glucagon secretion is stimulated.
细胞蛋白质生物合成受多种因素调控,但细胞间接触对α和β细胞蛋白质生物合成活性的影响尚未被研究。胰岛细胞的生物合成活性对于调节细胞内激素储备以及控制分泌所涉及的所有蛋白质的更新至关重要。在此,我们旨在评估细胞间相互作用是否会相似地影响大鼠α和β细胞的分泌和蛋白质生物合成。通过 ELISA 或反向溶血斑测定分析胰岛素和胰高血糖素的分泌,并用生物正交非天然氨基酸标记法在单细胞水平评估蛋白质生物合成。关于β细胞,我们发现胰岛素分泌与蛋白质生物合成之间存在正相关。我们还观察到,在低或中等葡萄糖浓度下,同源接触增加了这两种活性。相比之下,在高葡萄糖浓度下,同源接触增加了胰岛素分泌,但没有增加蛋白质生物合成。此外,β细胞和α细胞之间的异质接触对胰岛素分泌和蛋白质生物合成没有影响。关于α细胞,我们发现当它们与β细胞接触时,它们会在葡萄糖浓度下降时增加胰高血糖素的分泌,但另一方面,它们会在任何葡萄糖浓度下降低蛋白质生物合成。总的来说,这些结果强调了细胞间接触对胰岛细胞功能的作用,表明细胞间接触增加了β细胞的蛋白质生物合成,除了在高葡萄糖浓度下,还降低了α细胞的蛋白质生物合成,即使胰高血糖素分泌受到刺激。