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Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism.

ABSTRACT: 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 Fenneropenaeus merguiensis (Fm-RpL10a) could stimulate cell proliferation and trehalose metabolism in RpL10a-over-expressing flies by inducing insulin receptor (InR) expression and some insulin signaling mediators phosphorylation. In this study, we investigated the in silico binding between Fm-RpL10a and InR. The results indicated that Fm-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 Fm-RpL10a could stimulate glucose utilisation by insulin-resistant cells (IRCs) and healthy cells. Additionally, Fm-RpL10a at a low concentration (1 ?g/ml) altered some glucose metabolism-related genes expression in Fm-RpL10a treated IRCs. The qRT-PCR result revealed the up-regulation of Hk1, which encode key enzymes in glycolysis. Conversely, the expression of G6pc3, which participates in gluconeogenesis, was down-regulated. Overall, the results suggest that Fm-RpL10a can alleviate insulin resistance by stimulating insulin signaling via the FnIII2 domain of InR and activate glycolysis. Therefore, Fm-RpL10a may be a candidate insulin mimetic for the treatment of diabetes.

SUBMITTER: Chaichanit N

PROVIDER: S-EPMC7750378 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism.

Chaichanit Netnapa N Saetan Uraipan U Wonglapsuwan Monwadee M Chotigeat Wilaiwan W

Heliyon 20201215 12

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 Fenneropenaeus merguiensis (Fm-RpL10a) could stimulate cell proliferation and trehalose metabolism in RpL10a-over-expressing flies by inducing insulin receptor (< ...[more]

PMID: 33364490

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Project description:Glucose metabolism is under the cooperative regulation of both insulin receptor (IR) and ?(2)-adrenergic receptor (?(2)AR), which represent the receptor tyrosine kinases (RTKs) and seven transmembrane receptors (7TMRs), respectively. Studies demonstrating cross-talk between these two receptors and their endogenous coexpression have suggested their possible interactions. To evaluate the effect of IR and prospective heteromerization on ?(2)AR properties, we showed that IR coexpression had no effect on the ligand binding properties of ?(2)AR; however, IR reduced ?(2)AR surface expression and accelerated its internalization. Additionally, both receptors displayed a similar distribution pattern with a high degree of colocalization. To test the possible direct interaction between ?(2)AR and IR, we employed quantitative BRET(2) saturation and competition assays. Saturation assay data suggested constitutive ?(2)AR and IR homo- and heteromerization. Calculated acceptor/donor (AD50) values as a measure of the relative affinity for homo- and heteromer formation differed among the heteromers that could not be explained by a simple dimer model. In heterologous competition assays, a transient increase in the BRET(2) signal with a subsequent hyperbolical decrease was observed, suggesting higher-order heteromer formation. To complement the BRET(2) data, we employed the informational spectrum method (ISM), a virtual spectroscopy method to investigate protein-protein interactions. Computational peptide scanning of ?(2)AR and IR identified intracellular domains encompassing residues at the end of the 7th TM domain and C-terminal tail of ?(2)AR and a cytoplasmic part of the IR ? chain as prospective interaction domains. ISM further suggested a high probability of heteromer formation and homodimers as basic units engaged in heteromerization. In summary, our data suggest direct interaction and higher-order ?(2)AR:IR oligomer formation, likely comprising heteromers of homodimers.

Dataset Information

Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism.

Publications

Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism.

Similar Datasets

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