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

Efraim Westholm, Alexandros Karagiannopoulos, Nicole Kattner, Yara Al-Selwi, George Merces, James AM Shaw, Anna Wendt, Lena Eliasson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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
Originalspråkengelska
Artikelnummer110767
TidskriftiScience
Volym27
Nummer9
DOI
StatusPublished - 2024 aug. 19

Ämnesklassifikation (UKÄ)

  • Endokrinologi och diabetes

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