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Lookup NU author(s): Dr Nicole Kattner, Yara Al-Selwi, George Merces, Professor James Shaw
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)Intra-islet crosstalk has become a focus area to fully understand the regulation of insulin secretion and impaired β-cell function in type 2 diabetes (T2D). Here, we put forward evidence for insulin-like growth factor binding protein 7 (IGFBP7) as a potential protein involved in autocrine and paracrine β-cell regulation. We showed presence of IGFBP7 in granules of both human α- and β-cells and measured elevated gene expression as well as IGFBP7 protein in T2D. Insulin secretion was reduced in human islets, and the human β-cell line EndoC-βH1, after 72-h incubation with IGFBP7. Mechanistically reduced insulin secretion by IGFBP7 is attributed to reduced p21-activated kinase 1 (PAK1) protein, and decreased oxygen consumption and ATP-production. Knockdown of IGFBP7 in EndoC-βH1 cells verified reduced IGFBP7 levels in the medium, as well as improved insulin secretion. Finally, IGFBP7 knockdown in islets from T2D donors improved insulin secretion, making IGFBP7 a potential drug target in diabetes.
Author(s): Westholm E, Karagiannopoulos A, Kattner N, Al-Selwi Y, Merces G, Shaw JAM, Wendt A, Eliasson L
Publication type: Article
Publication status: Published
Journal: iScience
Year: 2024
Volume: 27
Issue: 9
Print publication date: 20/09/2024
Online publication date: 20/08/2024
Acceptance date: 15/08/2024
Date deposited: 11/11/2024
ISSN (electronic): 2589-0042
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.isci.2024.110767
DOI: 10.1016/j.isci.2024.110767
Data Access Statement: previously published islet RNA-seq data and donor characteristics used in Figures 1A–1D, S1A, and S1B can be accessed upon reasonable request to the lead contact of that work.19 The human islet RNA-seq dataset with or without treatment with IGFBP7 were deposited in the Lund University Diabetes Center (LUDC) repository (https://www.ludc.lu.se/resources/repository) under the following accession number LUDC IGFBP7 cohort (accession number LUDC2024.08.114), and is available from the lead contact (Lena Eliasson) upon request but access to data must be granted by the LUDC Human Tissue Laboratory steering committee. Individual-level data are not publicly available due to ethical and legal restrictions related to the Swedish Biobanks in Medical Care Act (2023:38) and Personal Data Act (1998:204). Summary statistics describing these data are presented in Table S3. Previously published scRNA-seq data used in Figure 4A can be found at (GEO: GSE153855) and is described in Ngara and Wierup.31
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