IGFBP7 is upregulated in islets from T2D donors and reduces insulin secretion
Year: 2024
Type: article
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.
Source: iScience
Institutions: Lund University, Skåne University Hospital, Newcastle University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Cystic Fibrosis Trust, Newcastle University, Stiftelsen för Strategisk Forskning, Vetenskapsrådet, Barndiabetesfonden, Kungliga Fysiografiska Sällskapet i Lund, Direktör Albert Påhlssons Stiftelse, Diabetesförbundet, Diabetesfonden, Stiftelsen Riksförbundet Cystisk Fibros Forskningsfond, Svenska Diabetesstiftelsen
OpenAlex ID: W4402158880