Fluorescent exendin-4 derivatives for pancreatic β-cell analysis
Open accessAbstract
The ability to reliably identify pancreatic β-cells would have far reaching implications for a greater understanding of β-cell biology, measurement of β-cell mass in diabetes, islet transplantation, and drug development. The glucagon-like peptide-1 receptor (GLP1R) is highly expressed on the surface of insulin producing pancreatic β-cells. Using systematic modifications of the GLP1R ligand, exendin-4, we screened over 25 compounds and identified a palette of fluorescent exendin-4 with high GLP1R binding affinity. We show considerable differences in affinity, as well as utility of the top candidates for flow cytometry and microscopy of β-cells. Some of the developed compounds should be particularly useful for basic and translational β-cell research.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Fluorescent exendin-4 derivatives should bind preferentially to β-cells.
“One promising approach is to use fluorescent exendin-4 derivatives, which should bind preferentially to β-cells ( 61 , 62 ).”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Eng, J., Kleinman, W. A., Singh, L., Singh, G., & Raufman, J. P. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42531-8 · Cited by 1,000 · see citing works
Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes
Åhrén, B. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2782 · Cited by 417 · see citing works
Panjwani, N., Mulvihill, E. E., Longuet, C., Yusta, B., Campbell, J. E., Brown, T. J., Streutker, C., Holland, D., Cao, X., Baggio, L. L., et al. (2013) · Endocrinology · doi:10.1210/en.2012-1937 · Cited by 346 · see citing works
Pancreatic beta cell lines and their applications in diabetes mellitus research
Skelin, M. (2010) · ALTEX · doi:10.14573/altex.2010.2.105 · Cited by 292 · see citing works
NIT-1, a Pancreatic β-Cell Line Established From a Transgenic NOD/Lt Mouse
Hamaguchi, K., Gaskins, H. R., & Leiter, E. H. (1991) · Diabetes · doi:10.2337/diab.40.7.842 · Cited by 259 · see citing works
Exendin-4–Based Radiopharmaceuticals for Glucagonlike Peptide-1 Receptor PET/CT and SPECT/CT
Wild, D., WICKI, A. N., Mansi, R., Béhé, M. P., Keil, B. R., Bernhardt, P., Christofori, G., Ell, P. J., & Mäcke, H. R. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.074914 · Cited by 155 · see citing works
Reiner, T., Thurber, G., Gaglia, J., Vinegoni, C., Liew, C. W., Upadhyay, R., Kohler, R. H., Li, L., Kulkarni, R. N., Benoist, C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109859108 · Cited by 120 · see citing works
Self-citation18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma
Kiesewetter, D. O., Gao, H., Ma, Y., Niu, G., Quan, Q., Guo, N., & Chen, X. S. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-011-1980-0 · Cited by 108 · see citing works
Islet cell analysis and purification by light scatter and autofluorescence
Winkel, M. V. D., Maes, E., & PIPELEERS, D. G. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(82)91523-6 · Cited by 100 · see citing works
In Vivo Imaging of Transplanted Islets with 64Cu-DO3A-VS-Cys40-Exendin-4 by Targeting GLP-1 Receptor
Wu, Z., Todorov, I., Li, C., Bading, J. R., Li, Z., Nair, I., Ishiyama, K., Colcher, D. M., Conti, P. E., Fraser, S. E., et al. (2011) · Bioconjugate Chemistry · doi:10.1021/bc200132t · Cited by 90 · see citing works
Gromada, J., Rorsman, P., Dissing, S., & Wulff, B. S. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)01070-u · Cited by 66 · see citing works
Kirkpatrick, A., Heo, J., Abrol, R., & Goddard, W. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218051109 · Cited by 54 · see citing works
Kim, T. H., Jiang, H. H., Lee, S., Youn, Y. S., Park, C. W., Byun, Y., Chen, X. S., & Lee, K. C. (2011) · Bioconjugate Chemistry · doi:10.1021/bc100404x · Cited by 53 · see citing works
Wang, Y., Lim, K., Normandin, M. D., Zhao, X., Cline, G. W., & Ding, Y. (2011) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2011.07.011 · Cited by 52 · see citing works
Efficient 18F‐Labeling of Synthetic Exendin‐4 Analogues for Imaging Beta Cells
Keliher, E. J., Reiner, T., Thurber, G. M., Upadhyay, R., & Weissleder, R. (2012) · ChemistryOpen · doi:10.1002/open.201200014 · Cited by 48 · see citing works
Self-citationGill, H. S., & Mařı́k, J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.390 · Cited by 46 · see citing works
Facile synthesis of monofunctional pentamethine carbocyanine fluorophores
Shao, F., Yuan, H., Josephson, L., Weissleder, R., & Hilderbrand, S. A. (2010) · Dyes and Pigments · doi:10.1016/j.dyepig.2010.12.008 · Cited by 29 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
Halban, P. A., Polonsky, K. S., Bowden, D. W., Hawkins, M. A., Ling, C., Mather, K. J., Powers, A. C., Rhodes, C. J., Sussel, L., & Weir, G. C. (2014) · Diabetes Care · doi:10.2337/dc14-0396 · Cited by 460 · see citing works
“which should bind preferentially to b-cells (61,62).”
Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation
McLean, B. A., Wong, C. K., Campbell, J. E., Hodson, D. J., Trapp, S., & Drucker, D. J. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa032 · Cited by 289 · see citing works
β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment
Halban, P. A., Polonsky, K. S., Bowden, D. W., Hawkins, M. A., Ling, C., Mather, K. J., Powers, A. C., Rhodes, C. J., Sussel, L., & Weir, G. C. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1425 · Cited by 228 · see citing works
Ast, J., Arvaniti, A., Fine, N. H. F., Nasteska, D., Ashford, F. B., Stamataki, Z., Kőszegi, Z., Bacon, A., Jones, B. J., Lucey, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14309-w · Cited by 135 · see citing works
Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis
Cameron-Vendrig, A., Adili, R., Siraj, M. A., Xu, X., Wang, Y., Lei, X., Afroze, T., Shikatani, E. A., El-Mounayri, O., Noyan, H., et al. (2016) · Diabetes · doi:10.2337/db15-1141 · Cited by 141 · see citing works
Self-citationEpigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells
Fu, W., Farache, J., Clardy, S. M., Hattori, K., Mander, P. K., Lee, K. C., Rioja, I., Weissleder, R., Prinjha, R. K., Benoist, C. O., et al. (2014) · eLife · doi:10.7554/elife.04631 · Cited by 83 · see citing works
Self-citationExendin‐4 analogs in insulinoma theranostics
Jansen, T. J. P., van Lith, S. A. M., Boss, M., Brom, M., Joosten, L., Béhé, M. P., Buitinga, M., & Gotthardt, M. (2019) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3750 · Cited by 78 · see citing works
Yap, M. K. K., & Misuan, N. (2018) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13169 · Cited by 77 · see citing works
In Vivo Imaging of GLP-1R with a Targeted Bimodal PET/Fluorescence Imaging Agent
Brand, C., Abdel-Atti, D., Zhang, Y., Carlin, S., Clardy, S. M., Keliher, E. J., Weber, W., Lewis, J. S., & Reiner, T. (2014) · Bioconjugate Chemistry · doi:10.1021/bc500178d · Cited by 58 · see citing works
Self-citationImaging the emergence and natural progression of spontaneous autoimmune diabetes
Mohan, J. F., Köhler, R. H., Hill, J. A., Weissleder, R., Mathis, D. J., & Benoist, C. O. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707381114 · Cited by 58 · see citing works
Self-citationMolecular imaging of β-cells: diabetes and beyond
Wei, W., Ehlerding, E. B., Lan, X., Luo, Q., & Cai, W. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.06.022 · Cited by 51 · see citing works
Reagents and models for detecting endogenous GLP1R and GIPR
Ast, J., Broichhagen, J., & Hodson, D. J. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103739 · Cited by 40 · see citing works
Development of a clickable bimodal fluorescent/PET probe for in vivo imaging
Paulus, A., Desai, P., Carney, B. D., Carlucci, G., Reiner, T., Brand, C., & Weber, W. (2015) · EJNMMI Research · doi:10.1186/s13550-015-0120-4 · Cited by 39 · see citing works
Lucey, M., Ashik, T., Marzook, A., Wang, Y., Goulding, J., Oishi, A., Broichhagen, J., Hodson, D. J., MINNION, J. S., Elani, Y., et al. (2021) · Molecular Pharmacology · doi:10.1124/molpharm.121.000270 · Cited by 37 · see citing works
Pancreatic β‐cell imaging in humans: fiction or option?
Laurent, D., Vinet, L., Lamprianou, S., Daval, M., Filhoulaud, G., Ktorza, A., Wang, H., Sewing, S., Juretschke, H. P., Glombik, H., et al. (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12544 · Cited by 37 · see citing works
Targets and probes for non-invasive imaging of β-cells
Jodal, A., Schibli, R., & Béhé, M. P. (2016) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-016-3592-1 · Cited by 34 · see citing works
Ast, J., Nasteska, D., Fine, N. H. F., Nieves, D. J., Kőszegi, Z., Lanoiselée, Y., Cuozzo, F., Viloria, K., Bacon, A., Luu, N. T., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35716-1 · Cited by 33 · see citing works
Fluorescence Imaging of Peripheral Nerves by a Nav1.7-Targeted Inhibitor Cystine Knot Peptide
Gonzales, J., França, P. D. D. S., Jiang, Y., Pirovano, G., Kossatz, S., Guru, N., Yarilin, D., Agwa, A. J., Schroeder, C. I., Patel, S. G., et al. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00612 · Cited by 31 · see citing works
Vinet, L., Lamprianou, S., Babič, A., Lange, N., Thorel, F., Herrera, P. L., Montet, X., & Meda, P. (2014) · Diabetologia · doi:10.1007/s00125-014-3442-2 · Cited by 27 · see citing works
Zhang, L., Navaratna, T. A., Liao, J., & Thurber, G. M. (2015) · Bioconjugate Chemistry · doi:10.1021/bc500584t · Cited by 27 · see citing works
Expanded LUXendin Color Palette for GLP1R Detection and Visualization In Vitro and In Vivo
Ast, J., Novak, A. N., Podewin, T., Fine, N. H. F., Jones, B. J., Tomás, A., Birke, R., Roßmann, K., Mathes, B., Eichhorst, J., et al. (2022) · JACS Au · doi:10.1021/jacsau.2c00130 · Cited by 24 · see citing works
Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes
Hu, M. L., Zhang, Y., Xiang, N., Zhong, Y., Gong, T., Zhang, Z., & Fu, Y. S. (2016) · Pharmaceutical Research · doi:10.1007/s11095-016-1873-9 · Cited by 20 · see citing works
Rapid, high efficiency isolation of pancreatic ß-cells
Clardy, S. M., Mohan, J. F., Vinegoni, C., Keliher, E. J., Iwamoto, Y., Benoist, C. O., Mathis, D. J., & Weissleder, R. (2015) · Scientific Reports · doi:10.1038/srep13681 · Cited by 18 · see citing works
Self-citationBerclaz, C., Pache, C., Bouwens, A., Szlag, D., Lopez, A., Joosten, L., Ekim, S., Brom, M., Gotthardt, M., Grapin‐Botton, A., et al. (2015) · Scientific Reports · doi:10.1038/srep10385 · Cited by 18 · see citing works
Lehtonen, J., Schäffer, L., Rasch, M. G., Hecksher‐Sørensen, J., & Ahnfelt‐Rønne, J. (2015) · Islets · doi:10.1080/19382014.2015.1137415 · Cited by 17 · see citing works
Li, D., Huang, Z., Chen, S., Hu, Z., & Li, W.-H. (2015) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.5b00332 · Cited by 17 · see citing works
In vitro imaging of β-cells using fluorescent cubic bicontinuous liquid crystalline nanoparticles
Miceli, V., Meli, V., Blanchard-Desce, M. H., Bsaibess, T., Pampalone, M., Conaldi, P. G., Caltagirone, C., Obiols‐Rabasa, M., Schmidt, J., Talmon, Y., et al. (2016) · RSC Advances · doi:10.1039/c6ra09616f · Cited by 14 · see citing works
Affinity-Driven Aryl Diazonium Labeling of Peptide Receptors on Living Cells
Sharma, S., Naldrett, M. J., Gill, M. J., & Checco, J. W. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c04672 · Cited by 11 · see citing works
Multivalent glibenclamide to generate islet specific imaging probes
Babič, A., Lamprianou, S., Vinet, L., Stransky-Heilkron, N., Xayaphoummine, C., Campo, M. A., Glombik, H., Schulte, A. M., Juretschke, H., Montet, X., et al. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.10.006 · Cited by 10 · see citing works
Dong, J., Zhou, X., Li, Q., Zheng, R., Chen, J., Liu, Y., Tong, X., Wan, Z., & Gong, T. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16070875 · Cited by 9 · see citing works
Optoacoustic Imaging of Glucagon-like Peptide-1 Receptor with a Near-Infrared Exendin-4 Analog
Roberts, S. S., Khera, E., Choi, C., Navaratna, T. A., Grimm, J., Thurber, G. M., & Reiner, T. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.252262 · Cited by 9 · see citing works
Squalene-PEG-Exendin as High-Affinity Constructs for Pancreatic Beta-Cells
Babič, A., Vinet, L., Chellakudam, V., Janikowska, K., Allémann, É., & Lange, N. (2018) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.8b00186 · Cited by 8 · see citing works
Targeted pancreatic beta cell imaging for early diagnosis
Goh, Z. C., Ghosh, K. K., Mishra, S., Gulyás, M., Kovács, T., Máthé, D., Padmanabhan, P., & Gulyás, B. Z. (2020) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2020.151110 · Cited by 7 · see citing works
In vivo functional profiling and structural characterization of the human GLP1R A316T variant
Eid, L. E., Manchanda, Y., Austin, G. O., Deane-Alder, K., Rujan, R., Mariam, Z., Oqua, A. I., Belousoff, M. J., de la Serna, J. B., Sloop, K. W., et al. (2026) · Science Advances · doi:10.1126/sciadv.adw0899 · Cited by 5 · see citing works
Two-photon imaging of pancreatic beta cells in real time in vivo
Clardy, S. M., Köhler, R. H., Vinegoni, C., Iwamoto, Y., Keliher, E. J., & Weissleder, R. (2016) · TECHNOLOGY · doi:10.1142/s2339547816200028 · Cited by 2 · see citing works
Self-citationGLP-1R is downregulated in beta cells of NOD mice and T1D patientsPreprint
Recino, A., Barkan, K., Schmidt-Christensen, A., Nilsson, J., Holmes, N., Howie, D., Holmberg, D., Larsson, P. G., Flodström‐Tullberg, M., Laraia, L., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/845776 · Cited by 2 · see citing works
In vivo functional profiling and structural characterisation of the human Glp1r A316T variantPreprint
Eid, L. E., Deane-Alder, K., Rujan, R., Mariam, Z., Oqua, A. I., Manchanda, Y., Belousoff, M. J., de la Serna, J. B., Sloop, K. W., Rutter, G. A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.19.619191 · Cited by 2 · see citing works
Cristelo, C., Nunes, R., Pinto, S. F. T., Marques, J. M., Gama, F. M., & Sarmento, B. (2023) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.1021/acsptsci.3c00218
Pacific Blue succinimidyl ester
Sabnis, R. W. (2015) · doi:10.1002/9781119007104.ch117
- Authors
- Clardy, S. M., Keliher, E. J., Mohan, J. F., Sebas, M., Benoist, C., Mathis, D., & Weissleder, R.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Weissleder, Ralph
- ORCID
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-12-20
- Volume
- 25
- Issue
- 1
- Pages
- 171-177
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- PMC
- PMC4016126
- OpenAlex
- W1996106696
- Cited by
- 41
- References
- 17
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 9 · 2014: 5
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bioconjugate Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Cancer Institute (T32-CA 79443, T32CA079443)
- National Institute of Allergy and Infectious Diseases (P01-AI54904, P01AI054904)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- exendin-4, fluorescent derivatives, pancreatic beta cells, GLP-1 receptor, beta-cell mass, islet transplantation, flow cytometry, fluorescence microscopy, ligand binding affinity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Cells, Cultured, Fluorescence, Humans, Mice, Inbred C57BL, Models, Molecular, Peptides, Venoms, Molecular Structure, Receptors, Glucagon, Insulin-Secreting Cells, Mice, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
