Blinded by the Light of Fluorescence in Beta Mass and Vessels
By: Alex Parrott
Everyone knows that the most common biomarkers for diabetes are the concentrations of insulin and glucose in the blood, but equally important is the beta cell mass. Since beta cells are what spark insulin development in the body, monitoring beta cell mass changes in diabetics can provide vital information on the progress of the disease over time. Dr. Kang and Dr. Nishimura have both made advances in beta cell mass imaging using two different but effective methods.
Dr. Kang’s team utilizes a multimodal probe to create an image of the beta mass in pancreas islet fluorescents (PiF) using positron emission tomography (PET). The imaging was done on streptozotocin (STZ)-treated mice models and involves administering a PiF stain to the beta cells by means of the tail vein.This method is a major advancement since previous processes like pancreas islet yellow(PiY) can take around 24 hours to be completed. To allow for fluorescent imaging, the PiF was composed via a diversity-oriented fluorescence library approach (DOFLA), which utilizes a series of thousands of fluorescent molecules combined with fluorine. After positive test results with fluorescent images, they replaced the fluorine with radioisotope fluorine 18 to allow for PET probe generation. All of their results conclude positively for PiF and resulted in higher per islet intensity then the previous PiY process.
Dr. Nishimura also looked at bioimaging the beta cell mass, but wanted to take into account the shape of the mass. Beta cell mechanisms are not fully understood, and since insulin secretion is not just affected by beta cell mass and function, the morphological structure of the vessels supplying blood to the beta cells should also be mapped. Since the pancreas and the beta cell mass both undergo a major change in diabetics, the morphology of the blood vessels should also undergo a change. Dr. Nishimura recognized that if a 3D image of the vascular structure around the beta cells was developed it could help with understanding what is happening during physiological and pathological situations. Using a mouse model that was given an artificial chromosome (BAC)-mafA promoter to drive the fluorescent protein Kusabira Orange, Dr. Nishimura had the means to get a bioimage, but he ran into the issue of disproportionate islet distribution. Using optical clearing by means of Sca/eS images of mature beta cell masses he was successful in implementing in situ microscopy.
But why does this matter?
The previous methods like PiY are not efficient enough for constant monitoring since they take over 24 hours to complete, are conducted through an operation, use histological analysis for studying the results, and involve an uneven islet distribution, thus rendering these methods as approximations. Dr. Kang’s results prove that the PiF is more efficient than PiY and is effective on healthy pancreases. The human transplant also is evidence that human islets can be introduced without antibody or genetic manipulation. Dr. Nishimura’s results are a major accomplishment since it allows for cell detection without affecting surrounding tissue structure. Both of these studies greatly affect how diabetes is monitored, before and after diagnosis. If we are able to monitor the beta cell mass morphology, we can better understand its effect on diabetes and better treat people early on. The use of optics and electrical systems in biomedical applications is growing at a rapid pace due to the vast applications and their ability to do many functions at once, such as multimodal microscopy. While there is still a ways to go before a lot of optical interfaces are brought to clinical use, the advances achieved thus far will make treating diseases and developing cures more attainable.
- Kang, Nam‐Young, et al. “Visualization and Isolation of Langerhans Islets by a Fluorescent Probe PiY.” Wiley Online Library, John Wiley & Sons, Ltd, 28 May 2013, onlinelibrary.wiley.com/doi/full/10.1002/ange.201302149.
- Vendrell M, Zhai D, Er JC, Chang YT. “Combinatorial strategies in fluorescent probe development”. Chem Rev. 2012 Aug 8;112(8):4391-420. doi: 10.1021/cr200355j. Epub 2012 May 23. PMID: 22616565.
- Malaisse, W J, et al. “Fate of 2-Deoxy-2-[18F]Fluoro-D-Glucose in Control and Diabetic Rats.” International Journal of Molecular Medicine, Spandidos Publications, 1 May 2000, www.spandidos-publications.com/10.3892/ijmm.5.5.525.
- Jiang, Lei, et al. “PET Probes beyond (18)F-FDG.” Journal of Biomedical Research, Editorial Department of Journal of Biomedical Research, Nov. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4250522/.
- UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. “Transcription Factor MafA.” UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics, 7 Oct. 2020, www.uniprot.org/uniprot/Q8NHW3.
- Hama, Hiroshi, et al. “Sca l ES: an Optical Clearing Palette for Biological Imaging.” Nature News, Nature Publishing Group, 14 Sept. 2015, www.nature.com/articles/nn.4107.