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 μg/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.