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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)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Beta-cell Mass; Glucagon-like Peptide-1; Blood-glucose Improves; Hyperglycemia; Receptor; Onset; Normalization; Pancreas
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 69, Issue: 11, Pages: 2246-2252 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)
Grants 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