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Nilsson, C.I.* ; Dumral, Ö.* ; Sánchez, G.* ; Xie, B.* ; Müller, A. ; Solimena, M. ; Ren, H.* ; Idevall-Hagren, O.*

Somatostatin triggers local cAMP and Ca2+ signaling in primary cilia to modulate pancreatic β-cell function.

EMBO J. 44, 1663-1691 (2025)
Verlagsversion Forschungsdaten DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Somatostatin, released from δ-cells within pancreatic islets of Langerhans, is one of the most important negative regulators of islet hormone secretion. We find that islet δ-cells are positioned near, and release somatostatin onto, primary cilia of the other islet cell types, including insulin-secreting β-cells. Somatostatin activates ciliary somatostatin receptors, resulting in rapid lowering of the ciliary cAMP concentration which in turn promotes more sustained nuclear translocation of the cilia-dependent transcription factor GLI2 through a mechanism that operates in parallel with the canonical Hedgehog pathway and depends on ciliary Ca2+ signaling. We also find that primary cilia length is reduced in islets from human donors with type-2 diabetes, which is associated with a reduction in interactions between δ-cells and cilia. Our findings show that islet cell primary cilia constitute an important target of somatostatin action, which endows somatostatin with the ability to regulate islet cell function beyond acute suppression of hormone release.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hedgehog ; Protein Kinase A ; Type-2 Diabetes ; δ-cell; Delta-cells; Insulin-secretion; Hedgehog; Receptor; Expression; Alpha; Phosphorylation; Homeostasis; Homeobox-1; Platform
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 44, Heft: 6, Seiten: 1663-1691 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pancreatic Islet Research (IPI)
Förderungen Exodiab
Diabetes Wellness Sweden
European Foundation for the Study of Diabetes/Lilly
Family Ernfors Foundation
Swedish Diabetes Foundation
Novo-Nordisk Foundation
Swedish Research Council
Vetenskapsrdet (VR)