@article{d730deb78ce84a09ba1bce9efc172091,
title = "Noninvasive Monitoring of Glycemia-Induced Regulation of GLP-1R Expression in Murine and Human Islets of Langerhans",
abstract = "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.",
keywords = "BETA-CELL MASS, GLUCAGON-LIKE PEPTIDE-1, BLOOD-GLUCOSE IMPROVES, HYPERGLYCEMIA, RECEPTOR, ONSET, NORMALIZATION, PANCREAS",
author = "Mijke Buitinga and Cohrs, {Christian M.} and Eter, {Wael A.} and Lieke Claessens-Joosten and Cathelijne Frielink and Desiree Bos and Gerwin Sandker and Maarten Brom and Stephan Speier and Martin Gotthardt",
note = "Funding Information: Acknowledgments. The authors thank the animal technicians for their assistance in animal care and data collection. Funding. This project is supported by FP7 Coordination of Non-Community Research Programmes (BetaCure/602812); Paul Langerhans Institute Dresden (PLID) of Helmholtz Zentrum M{\"u}nchen at the University Clinic Carl Gustav Carus of Technische Universit{\"a}t Dresden; the German Ministry for Education and Research (BMBF) to the German Centre for Diabetes Research (DZD), and Deutsche Forschungsgemeinschaft-Sonderforschungsbereich (DFG-SFB)/Transregio 127; and it has received funding from the IMI 2 joint undertaking (INNODIA/115797 and INNODIA HARVEST 945268). This joint undertaking receives support from the Union{\textquoteright}s Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations (EFPIA), JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. Duality of Interest. M.G. declares that he is an inventor and holder of the patent “Invention affecting GLP-1 and exendin” (Philipps-Universit{\"a}t Marburg, June 17, 2009). No other potential conflicts of interest relevant to this article were reported. Author Contributions. M.Bu., C.M.C., and W.A.E. contributed to the design and conduct of the study and the analysis and interpretation of the data. M.Bu. and C.M.C. wrote and edited the manuscript. L.C.-J., C.F., D.B., and G.S. provided technical assistance in radiolabeling, tissue sectioning, immunostaining, and imaging. M.Br., S.S., and M.G. contributed to the experimental design, interpretation of the results, and conceptualization of the manuscript. S.S. and M.G. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this work were given as an oral presentation at the European Association of Nuclear Medicine, Barcelona, Spain, 15–19 October 2016; as a poster presentation at the European Association for the Study of Diabetes, Munich, Germany, 12–16 September 2016; and as a poster presentation at the 2nd Joint Meeting of the European Association for the Study of Diabetes Islet Study Group and Beta Cell Workshop, Dresden, Germany, 7–10 May 2017. Funding Information: This project is supported by FP7 Coordination of Non-Community Research Programmes (BetaCure/602812); Paul Langerhans Institute Dresden (PLID) of Helmholtz Zentrum M?nchen at the University Clinic Carl Gustav Carus of Technische Universit?t Dresden; the German Ministry for Education and Research (BMBF) to the German Centre for Diabetes Research (DZD), and Deutsche Forschungsgemeinschaft-Sonderforschungsbereich (DFG-SFB)/Transregio 127; and it has received funding from the IMI 2 joint undertaking (INNODIA/115797 and INNODIA HARVEST 945268). This joint undertaking receives support from the Union?s Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations (EFPIA), JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. Publisher Copyright: {\textcopyright} 2020 by the American Diabetes Association.",
year = "2020",
month = nov,
doi = "10.2337/db20-0616",
language = "English",
volume = "69",
pages = "2246--2252",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "11",
}