University of California Davis
University of Cincinnati Medical Center
University of Massachusetts Medical School
University of Michigan Medical School
Vanderbilt University School of Medicine
Protocols & Methods
Reagents & Resources
Tissues & Samples
Conditions of Use
Data Usage Policy
Tracers in Metabolic Research
Isotope Tracers in Metabolic Research: 3-Part Webinar Series
Energy Expenditure Analysis
CalR: Indirect Calorimetry Analysis
Guidelines & Policies
Characterization of viral insulins reveals white adipose tissue-specific effects
Chrudinová M, Moreau F, Noh HL, Páníková T, Žáková L, Friedline RH, Valenzuela
FA, Kim JK, Jirácek J, Kahn CR, Altindis E
Submitted Externally on 2/22/2021
Volume : Pages
44 : 101121
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 receptor (IR-A and IR-B) and to the IGF1R, and for the latter,
show higher affinity than human insulin. These dcVILPs stimulate IR and IGF1R
phosphorylation and post-receptor signaling in vitro and in vivo. Both GIV and
SGIV dcVILPs stimulate glucose uptake in mice. In vivo infusion experiments
revealed that while insulin (0.015 nmol/kg/min) and GIV dcVILP
(0.75 nmol/kg/min) stimulated a comparable glucose uptake in heart and skeletal
muscle and brown adipose tissue, GIV dcVILP stimulated 2-fold higher glucose
uptake in white adipose tissue (WAT) compared to insulin. This was associated
with increased Akt phosphorylation and glucose transporter type 4 (GLUT4) gene
expression compared to insulin in WAT., Our results show that GIV and SGIV
dcVILPs are active members of the insulin superfamily with unique
characteristics. Elucidating the mechanism of tissue specificity for GIV dcVILP
will help us to better understand insulin action, design new analogs that
specifically target the tissues and provide new insights into their potential
role in disease.
Back to Top
There was a problem with the page:
Safari Browser Detected...
We strive to make the MMPC site compatable with as many browsers as possible, but some of our third party tools don't work with the Safari browser.
In order to explore this site we highly recommend using the most recent versions of the following browsers:
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the MMPC using the following text:
Financial support for this work was provided by the NIDDK Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
) under the MICROMouse Program, grants DK076169.
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!
Warranty disclaimer and copyright notice
THE NATIONAL MMPC MAKES NO REPRESENTATION ABOUT THE SUITABILITY OR ACCURACY OF THE SOFTWARE OR DATA FOR ANY PURPOSE, AND MAKES NO WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR THAT THE USE OF THE SOFTWARE OR DATA WILL NOT INFRINGE ANY THIRD PARTY PATENTS, COPYRIGHTS, TRADEMARKS, OR OTHER RIGHTS. THE SOFTWARE AND DATA ARE PROVIDED "AS IS".
The Mouse Metabolic Phenotyping Centers (MMPC) is an NIDDK funded consortium and adheres to the
NIH Data Sharing Policy
MMPC clients make their data freely available whereby MMPC users may freely build upon, enhance and reuse those data for any purpose without restriction. Scholarly citation norms must be followed for content reuse. Please acknowledge the MMPC using the following text: 'The MMPC data used in this manuscript was supported by the NIDDK National Mouse Metabolic Phenotyping Centers (National MMPC, RRID:SCR_008997,
)'. To cite specific MMPC centers, please use the appropriate RRID available from the MMPC website (
Please note that the acknowledgment text includes a Research Resource Identifier (RRID) for the MMPC CU and Centers. Reproducibility is one of the corner stones of effective, open and transparent biomedical published research. However, too often, resources (e.g. model organisms, antibodies, and tools) are not reported with adequate detail to ensure others can replicate or expand upon the published results. The Research Resource Identification Initiative (#RII) seeks to change these limitations in reporting by the use of unique Research Resource Identifiers (RRIDs). This initiative is designed to encourage authors to provide identification of the types of resources used in their research by adding a globally unique accession number to the resources described in the their manuscripts. These identifiers, called RRIDs, will allow authors to cite the resources that they use in their manuscripts. RRIDs allow for easy tracking of all papers that have used the same resource making it easy to access how the same resources works in other scenarios.
It is expected that MMPC users follow scholarly citation norms, giving credit to fellow scholars when accessing/using protocols and data, including data derived by MMPC (such as summary data) and any plots, tables or screenshots depicting those data.
It is possible for invalid or incomplete results to be presented on the MMPC web site due to software bugs, data problems, or artifacts of human error. Data sets are not necessarily static; we reserve the right to post corrections and updates as needed.
Data contributors and data users may not use MMPC in any unlawful manner, or in any manner that could impair MMPC services, security or functionality. Automated usage (webcrawlers and similar) must observe each page's "meta robots" html tags and space requests by ≥ 2 seconds. We reserve the right to block any IP associated with what we consider to be excessive or abusive usage patterns, and/or to take any action we deem necessary.
The MMPC is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.
Interested in receiving MMPC News?
2017 National MMPC. All Rights Reserved.