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IGFBP7 is upregulated in islets from T2D donors and reduces insulin secretion

Westholm, Efraim LU ; Karagiannopoulos, Alexandros LU orcid ; Kattner, Nicole ; Al-Selwi, Yara ; Merces, George ; Shaw, James AM ; Wendt, Anna LU and Eliasson, Lena LU orcid (2024) In iScience 27(9).
Abstract
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... (More)
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 (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
iScience
volume
27
issue
9
article number
110767
publisher
Elsevier
external identifiers
  • pmid:39280605
  • scopus:85207372491
ISSN
2589-0042
DOI
10.1016/j.isci.2024.110767
language
English
LU publication?
yes
id
7b0e7f65-098e-46a0-9baf-c171bd5ef66a
date added to LUP
2024-10-22 11:04:21
date last changed
2025-04-04 15:11:45
@article{7b0e7f65-098e-46a0-9baf-c171bd5ef66a,
  abstract     = {{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       = {{Westholm, Efraim and Karagiannopoulos, Alexandros and Kattner, Nicole and Al-Selwi, Yara and Merces, George and Shaw, James AM and Wendt, Anna and Eliasson, Lena}},
  issn         = {{2589-0042}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{9}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{IGFBP7 is upregulated in islets from T2D donors and reduces insulin secretion}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2024.110767}},
  doi          = {{10.1016/j.isci.2024.110767}},
  volume       = {{27}},
  year         = {{2024}},
}