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Lorza-Gil, E. ; Gerst, F. ; Oquendo, M.B.* ; Deschl, U.* ; Häring, H.-U. ; Beilmann, M.* ; Ullrich, S.

Glucose, adrenaline and palmitate antagonistically regulate insulin and glucagon secretion in human pseudoislets.

Sci. Rep. 9:10261 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Isolated human islets do not always meet the quality standards required for transplant survival and reliable functional in vitro studies. The formation of pseudoislets, i.e. the reaggregation of a defined number of islet cells after dissociation, improves insulin secretion. We present a simple method of pseudoislet formation from human islet cells and assess the transcriptome and function of isolated human islets and pseudoislets from the same organ donors. Following pseudoislet formation, insulin content/DNA and mRNA/RPS13 resembled that of islets. In pseudoislets, glucose-stimulated insulin secretion (GSIS) was significantly higher (8-13-fold) than in islets (2-4-fold). GSIS of pseudoislets was partly inhibited by the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin-9. The stimulatory effects of palmitate and forskolin at 12 mM glucose were also significantly higher in pseudoislets than in islets. Further analysis of pseudoislets revealed that regulation of secretion and insulin and glucagon content was maintained over a longer culture period (6-14 d). While adrenaline inhibited GSIS, adrenaline together with palmitate stimulated glucagon secretion 2-fold at low glucose, an effect suppressed by high glucose. Transcriptome analysis revealed that, unlike islets, pseudoislets were deprived of exocrine and endothelial cells. In conclusion, pseudoislet formation restores functional integrity of human islet cells and allows long-term in vitro testing.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Human Pancreatic-islets; Human Beta-cells; Rat Islets; Inhibition; Architecture; Relevance; Pathways; Receptor; Release; Health
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 10261 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)