ArticleProceedings of the National Academy of Sciences of the United States of America2011
Accurate measurement of pancreatic islet beta-cell mass using a second-generation fluorescent exendin-4 analog.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Insulin gene mutations and posttranslational and translocation defects: associations with diabetes.Endocrine · 2020Pooled it
- Engineered GLP-1R-targeting nanoplatforms: multimodal therapeutics in human diseases.Journal of nanobiotechnology · 2025Review
- Fluorescent probes in autoimmune disease research: current status and future prospects.Journal of translational medicine · 2025Review
- Diabetology and Nanotechnology: A Compelling Combination.Recent patents on nanotechnology · 2025Review
- Bibliometric analysis of research on the utilization of nanotechnology in diabetes mellitus and its complications.Nanomedicine (London, England) · 2024Article
- The anterior chamber of the eye technology and its anatomical, optical, and immunological bases.Physiological reviews · 2024Review
- B-Glycine as a marker for β cell imaging and β cell mass evaluation.European journal of nuclear medicine and molecular imaging · 2024Article
- NabioRxiv : the preprint server for biology · 2024Article
- Development and Validation of Nerve-Targeted Bacteriochlorin Sensors.Journal of the American Chemical Society · 2023Article
- Role of Exendin-4 Functional Imaging in Diagnosis of Insulinoma: A Systematic Review.Life (Basel, Switzerland) · 2023Review
- Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies.Diabetes · 2023Article
- Reagents and models for detecting endogenous GLP1R and GIPR.EBioMedicine · 2021Review
- Optoacoustic Imaging of Glucagon-like Peptide-1 Receptor with a Near-Infrared Exendin-4 Analog.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- State-of-the-art microscopy to understand islets of Langerhans: what to expect next?Immunology and cell biology · 2021Review
- Bimodal Imaging of Mouse Peripheral Nerves with Chlorin Tracers.Molecular pharmaceutics · 2021Article
- Metabolic Messengers: glucagon-like peptide 1.Nature metabolism · 2021Review
- Imaging Beta-Cell Function in the Pancreas of Non-Human Primates Using a Zinc-Sensitive MRI Contrast Agent.Frontiers in endocrinology · 2021Article
- Targeted Optical Imaging of the Glucagonlike Peptide 1 Receptor Using Exendin-4-IRDye 800CW.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Article
- Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.Dalton transactions (Cambridge, England : 2003) · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The hallmark of type 1 diabetes is autoimmune destruction of the insulin-producing β-cells of the pancreatic islets. Autoimmune diabetes has been difficult to study or treat because it is not usually diagnosed until substantial β-cell loss has already occurred. Imaging agents that permit noninvasive visualization of changes in β-cell mass remain a high-priority goal. We report on the development and testing of a near-infrared fluorescent β-cell imaging agent. Based on the amino acid sequence of exendin-4, we created a neopeptide via introduction of an unnatural amino acid at the K(12) position, which could subsequently be conjugated to fluorophores via bioorthogonal copper-catalyzed click-chemistry. Cell assays confirmed that the resulting fluorescent probe (E4(×12)-VT750) had a high binding affinity (~3 nM). Its in vivo properties were evaluated using high-resolution intravital imaging, histology, whole-pancreas visualization, and endoscopic imaging. According to intravital microscopy, the probe rapidly bound to β-cells and, as demonstrated by confocal microscopy, it was internalized. Histology of the whole pancreas showed a close correspondence between fluorescence and insulin staining, and there was an excellent correlation between imaging signals and β-cell mass in mice treated with streptozotocin, a β-cell toxin. Individual islets could also be visualized by endoscopic imaging. In short, E4(×12)-VT750 showed strong and selective binding to glucose-like peptide-1 receptors and permitted accurate measurement of β-cell mass in both diabetic and nondiabetic mice. This near-infrared imaging probe, as well as future radioisotope-labeled versions of it, should prove to be important tools for monitoring diabetes, progression, and treatment in both experimental and clinical contexts.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.