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Sequential and Asynchronous Strengthening of the Influence of Temperature on the Endo- and Exocytosis of Insulin in the Isolated Vertebrata Hepatocytes: Summing up Previous Studies.
Current Protein & Peptide Science ( IF 1.9 ) Pub Date : 2020-01-01 , DOI: 10.2174/1389203720666190325101804
Alexander P Kolychev 1 , Maxim A Terpilovskii 1 , Vladimir N Uversky 2, 3
Affiliation  

Insulin internalization and processing of the Insulin Receptor Complex (IRC) inside the cell are important components of the intracellular Mechanism of Insulin Action (MIA). They define the continuation of intracellular signaling of IRC and allow utilization of the parts of the complex after ligand dissociation. Traditionally, changes in the insulin regulatory system associated with the vertebrate phylogenesis have been evaluated by changes of its two elements: the hormone and its receptor. A hormone-competent cell was considered as an evolutionarily completed element of insulin regulatory system. However, previous studies of the isolated hepatocytes of four classes of vertebrates (lamprey, frog, chicken, and rat) revealed significant differences in the state of internalization of 125I-insulin and intracellular IRC processing. Radical differences were noted in the regulation of 125I-insulin internalization and the intracellular fate of the IRC. Here, cytosolic efficient insulin degradation and a complete lack of 125I-insulin exocytosis were observed in the cyclostome cells, whereas in amphibians the hormone underwent lysosomal degradation and showed low levels of exocytosis, while birds and mammals were characterized by high volumes of the excreted 125Iinsulin containing proteolytic 125I-insulin fragments. Despite the established recognition of the importance of the temperature factor, a complete understanding of the molecular mechanisms underlying the temperature effects on MIA is still missing. This poorly studied problem of the MIA temperature dependence can be behind the differences in the effect of temperature on the intracellular action of insulin and IGF-I. In fact, at different phylogenetic stages, successive changes were reported for the temperature dependence of the 125Iinsulin internalization and exocytosis. The following regularities were reported for the effect of temperature on the 125I-insulin internalization in isolated hepatocytes of different origin: complete lack of receptibility of the process to temperature in lampreys, receptibility of the process in a narrow range of low temperatures (0-5°C) in amphibians, and flexible regulation of 125I-insulin internalization in a wide temperature range (6- 37°C) in the cells from endothermic organisms. Reported data make it possible to observe three stages in the alteration of temperature regulation of 125I-insulin internalization (in cells of cyclostomes, amphibians, and endothermic organisms) and two stages of temperature regulation of 125I-insulin exocytosis in cells of amphibians, birds, and mammals. The data presented in this study reflect the specificity of the developmental reorganization of the intracellular MIA regulation and hormone utilization, and emphasize the central role of temperature in selective MIA formation during vertebrate phylogenesis.

中文翻译:

温度对分离的椎骨肝细胞中胰岛素内吞和胞吐作用的影响的顺序和异步增强:总结以前的研究。

细胞内部的胰岛素内在化和胰岛素受体复合物(IRC)的加工是细胞内胰岛素作用机制(MIA)的重要组成部分。它们定义了IRC的细胞内信号传导的延续,并允许配体解离后利用复合物的各个部分。传统上,与脊椎动物系统发育相关的胰岛素调节系统的变化已通过其两个要素的变化来评估:激素及其受体。具有激素能力的细胞被认为是胰岛素调节系统的进化完成要素。但是,先前对四类脊椎动物(七rey鳗,青蛙,鸡和大鼠)分离出的肝细胞的研究表明,125I-胰岛素的内在化状态和细胞内IRC加工状态存在显着差异。在125 I-胰岛素内在化的调节和IRC的细胞内命运方面存在根本差异。在这里,在环胃细胞中观察到了胞质有效的胰岛素降解和125I胰岛素胞外分泌的完全缺乏,而在两栖动物中,激素经历了溶酶体降解并显示出较低的胞吐作用,而鸟类和哺乳动物的特征是分泌了大量的125I胰岛素。含有蛋白水解的125I-胰岛素片段。尽管已公认温度因子的重要性,但仍缺少对温度对MIA影响的分子机制的完整理解。对MIA温度依赖性的研究不足,可能是温度对胰岛素和IGF-I细胞内作用的影响不同所致。实际上,在不同的系统发育阶段,据报道125I胰岛素内在化和胞吐作用的温度依赖性连续变化。对于温度对不同来源的分离的肝细胞中125I-胰岛素内在化的影响,报告了以下规律:完全缺乏七lamp鳗对温度的接受能力,在狭窄的低温范围内对过程的接受能力(0-5两栖动物),并在广泛的温度范围(6- 37°C)中对吸热生物体细胞中125I-胰岛素的内在化进行灵活调节。报告的数据可以观察到125I胰岛素内在化温度调节变化的三个阶段(在环网菌,两栖动物,和吸热生物)和两栖动物,鸟类和哺乳动物细胞中125 I-胰岛素胞吐作用的温度调节的两个阶段。这项研究中提供的数据反映了细胞内MIA调控和激素利用的发育重组的特异性,并强调了温度在脊椎动物系统发生过程中选择性MIA形成中的核心作用。
更新日期:2019-11-01
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