Buitinga, M.* ; Cohrs, C.M. ; Eter, W.A.* ; Claessens-Joosten, L.* ; Frielink, C.* ; Bos, D.* ; Sandker, G.* ; Brom, M.* ; Speier, S. ; Gotthardt, M.*
Non-invasive monitoring of glycemia-induced regulation of GLP-1R expression in murine and human islets of Langerhans.
Diabetes 69, 2246-2252 (2020)
Glucagon-like peptide 1 receptor (GLP-1R) imaging with radiolabeled exendin has proven to be a powerful tool to quantify beta-cell mass (BCM) in vivo. As GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose (BG) levels on GLP-1R-mediated exendin uptake in both murine and human islets and its implications for BCM quantification. Periods of hyperglycemia significantly reduced exendin uptake in murine and human islets, which was paralleled by a reduction in GLP-1R expression. Detailed mapping of the tracer uptake and insulin and GLP-1R expression conclusively demonstrated that the observed reduction in tracer uptake directly correlates to GLP-1R expression levels. Importantly, the linear correlation between tracer uptake and beta-cell area was maintained in spite of the reduced GLP-1R expression levels. Subsequent normalization of BG levels restored absolute tracer uptake and GLP-1R expression in beta-cells and the observed loss in islet volume was halted. This manuscript emphasizes the potency of nuclear imaging techniques to monitor receptor regulation noninvasively. Our findings have significant implications for clinical practice, indicating that BG levels should be near-normalized for at least 3 weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.
Impact Factor
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Times Cited
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Cited By
Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Beta-cell Mass; Glucagon-like Peptide-1; Blood-glucose Improves; Hyperglycemia; Receptor; Onset; Normalization; Pancreas
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2020
Prepublished im Jahr
HGF-Berichtsjahr
2020
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 69,
Heft: 11,
Seiten: 2246-2252
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-005
Förderungen
Leona M. and Harry B. Helmsley Charitable Trust
Paul Langerhans Institute Dresden (PLID) of Helmholtz Zentrum Munchen at the University Clinic Carl Gustav Carus of Technische Universitat Dresden
German Ministry for Education and Research (BMBF)
Deutsche Forschungsgemeinschaft-Sonderforschungsbereich (DFG-SFB)/Transregio 127
IMI 2 joint undertaking
Union's Horizon 2020 research and innovation programme
European Federation of Pharmaceutical Industries and Associations (EFPIA)
JDRF
FP7 Coordination of Non-Community Research Programmes
Copyright
Erfassungsdatum
2020-10-21