Haywood, NJ orcid.org/0000-0002-8762-7257, Cordell, PA, Tang, KY et al. (8 more authors) (2017) Insulin-Like Growth Factor Binding Protein 1 Could Improve Glucose Regulation and Insulin Sensitivity Through Its RGD Domain. Diabetes, 66 (2). pp. 287-299. ISSN 0012-1797
Abstract
Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation. The RGD integrin-binding domain of IGFBP-1, through integrin engagement, focal adhesion kinase, and integrin-linked kinase, enhanced insulin sensitivity and insulin secretion in C2C12 myotubes and INS-1 832/13 pancreatic β-cells. Both acute administration and chronic infusion of an RGD synthetic peptide to obese C57BL/6 mice improved glucose clearance and insulin sensitivity. These favorable effects on metabolic homeostasis suggest that the RGD integrin-binding domain of IGFBP-1 may be a promising candidate for therapeutic development in the field of insulin resistance.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Funding Information: | Funder Grant number EU - European Union 310747 British Heart Foundation PG/12/56/29748 |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Feb 2017 11:35 |
Last Modified: | 27 Jul 2018 15:24 |
Published Version: | https://doi.org/10.2337/db16-0997 |
Status: | Published |
Publisher: | American Diabetes Association |
Identification Number: | 10.2337/db16-0997 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112500 |