Characterization of viral insulins reveals white adipose tissue-specific effects in mice.

Molecular Metabolism
M. ChrudinovaEmrah Altindis

Abstract

Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 (LCDV-1) for the first time. The dcVILPs were chemically synthesized. Using murine fibroblast cell lines overexpressing insulin receptor (IR-A or IR-B) or IGF1R, we first determined the binding affinity of dcVILPs to the receptors and characterized post-receptor signaling. Further, we used C57BL/6J mice to study the effect of dcVILPs on lowering blood glucose. We designed a 3-h dcVILP in vivo infusion experiment to determine the glucose uptake in different tissues. GIV and SGIV dcVILPs bind to both isoforms of human insulin recept...Continue Reading

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Citations

Apr 20, 2021·Frontiers in Endocrinology·David M Irwin
Sep 30, 2021·Annual Review of Virology·Khyati GirdharEmrah Altindis
Oct 1, 2021·Journal of Medicinal Chemistry·Terezie PáníkováJiří Jiráček

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Methods Mentioned

BETA
protein folding
Assay
electrophoresis

Software Mentioned

Clustal Omega
ImageJ

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