Chaichanit Netnapa, Saetan Uraipan, Wonglapsuwan Monwadee, Chotigeat Wilaiwan
Department of Molecular Biotechnology and Bioinformatics, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla, 90112, Thailand.
Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla, 90112, Thailand.
Heliyon. 2020 Dec 15;6(12):e05714. doi: 10.1016/j.heliyon.2020.e05714. eCollection 2020 Dec.
The number of patients with insulin-resistant diabetes has significantly increased. Thus, alternative insulin mimetics are required for such patients. Some evidences indicate that ribosomal protein L10a (RpL10a) is involved in the insulin pathway. In addition, we previously demonstrated that recombinant RpL10a from (-RpL10a) could stimulate cell proliferation and trehalose metabolism in RpL10a-over-expressing flies by inducing () expression and some insulin signaling mediators phosphorylation. In this study, we investigated the binding between -RpL10a and InR. The results indicated that -RpL10a bound to InR at residues 635-640 and 697-702 of the FnIII2 domain. This binding was confirmed using a pull-down and immunofluorescence assay. Further analysis indicated that -RpL10a could stimulate glucose utilisation by insulin-resistant cells (IRCs) and healthy cells. Additionally, -RpL10a at a low concentration (1 μg/ml) altered some glucose metabolism-related genes expression in -RpL10a treated IRCs. The qRT-PCR result revealed the up-regulation of , which encode key enzymes in glycolysis. Conversely, the expression of , which participates in gluconeogenesis, was down-regulated. Overall, the results suggest that -RpL10a can alleviate insulin resistance by stimulating insulin signaling via the FnIII2 domain of InR and activate glycolysis. Therefore, -RpL10a may be a candidate insulin mimetic for the treatment of diabetes.
胰岛素抵抗型糖尿病患者的数量显著增加。因此，这类患者需要替代胰岛素模拟物。一些证据表明核糖体蛋白L10a（RpL10a）参与胰岛素信号通路。此外，我们之前证明来自（-RpL10a）的重组RpL10a可通过诱导（）表达和一些胰岛素信号介质磷酸化来刺激RpL10a过表达果蝇的细胞增殖和海藻糖代谢。在本研究中，我们研究了-RpL10a与InR之间的结合。结果表明-RpL10a与FnIII2结构域中第635 - 640位和第697 - 702位残基处的InR结合。通过下拉实验和免疫荧光分析证实了这种结合。进一步分析表明-RpL10a可刺激胰岛素抵抗细胞（IRC）和健康细胞的葡萄糖利用。此外，低浓度（1μg/ml）的-RpL10a改变了-RpL10a处理的IRC中一些与葡萄糖代谢相关基因的表达。qRT-PCR结果显示，编码糖酵解关键酶的（）上调。相反，参与糖异生的（）表达下调。总体而言，结果表明-RpL10a可通过InR的FnIII2结构域刺激胰岛素信号来减轻胰岛素抵抗并激活糖酵解。因此，-RpL10a可能是治疗糖尿病的候选胰岛素模拟物。
