Browsing by Subject "Endocrine system and metabolic diseases"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Author Correction: Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics
    (Nature Publishing Group, 2020-10-09) Ast, Julia; Arvaniti, Anastasia; Fine, Nicholas H. F.; Nasteska, Daniela; Ashford, Fiona B.; Stamataki, Zania; Koszegi, Zsombor; Bacon, Andrea; Jones, Ben J.; Lucey, Maria A.; Sasaki, Shugo; Brierley, Daniel I.; Hastoy, Benoit; Tomas, Alejandra; D’Agostino, Giuseppe; Reimann, Frank; Lynn, Francis C.; Reissaus, Christopher A.; Linnemann, Amelia K.; D’Este, Elisa; Calebiro, Davide; Trapp, Stefan; Johnsson, Kai; Podewin, Tom; Broichhagen, Johannes; Hodson, David J.; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats
    (Springer Nature, 2019-05-28) Vorland, Colby J.; Lachcik, Pamela J.; Swallow, Elizabeth A.; Metzger, Corinne E.; Allen, Matthew R.; Chen, Neal X.; Moe, Sharon M.; Hill Gallant, Kathleen M.; Anatomy and Cell Biology, IU School of Medicine
    Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.
  • Thumbnail Image
    Item
    Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review
    (Springer Nature, 2024-04-06) Felton, Jamie L.; Redondo, Maria J.; Oram, Richard A.; Speake, Cate; Long, S. Alice; Onengut-Gumuscu, Suna; Rich, Stephen S.; Monaco, Gabriela S. F.; Harris-Kawano, Arianna; Perez, Dianna; Saeed, Zeb; Hoag, Benjamin; Jain, Rashmi; Evans-Molina, Carmella; DiMeglio, Linda A.; Ismail, Heba M.; Dabelea, Dana; Johnson, Randi K.; Urazbayeva, Marzhan; Wentworth, John M.; Griffin, Kurt J.; Sims, Emily K.; ADA/EASD PMDI; Pediatrics, School of Medicine
    Background: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies. Methods: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment. Results: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation. Conclusions: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops.
  • Thumbnail Image
    Item
    Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics
    (Nature Research, 2020-01-24) Ast, Julia; Arvaniti, Anastasia; Fine, Nicholas H. F.; Nasteska, Daniela; Ashford, Fiona B.; Stamataki, Zania; Zania, Zsombor; Bacon, Andrea; Jones, Ben J.; Lucey, Maria A.; Sasaki, Shugo; Brierley, Daniel I.; Hastoy, Benoit; Tomas, Alejandra; D’Agostino, Giuseppe; Reimann, Frank; Lynn, Francis C.; Reissaus, Christopher A.; Linnemann, Amelia K.; D’Este, Elisa; Calebiro, Davide; Trapp, Stefan; Johnsson, Kai; Podewin, Tom; Broichhagen, Johannes; Hodson, David J.; Pediatrics, School of Medicine
    The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXendin645 produces intense and specific membrane labeling throughout live and fixed tissue. GLP1R signaling can additionally be evoked when the receptor is allosterically modulated in the presence of LUXendin645. Using LUXendin645 and LUXendin651, we describe islet, brain and hESC-derived β-like cell GLP1R expression patterns, reveal higher-order GLP1R organization including membrane nanodomains, and track single receptor subpopulations. We furthermore show that the LUXendin backbone can be optimized for intravital two-photon imaging by installing a red fluorophore. Thus, our super-resolution compatible labeling probes allow visualization of endogenous GLP1R, and provide insight into class B GPCR distribution and dynamics both in vitro and in vivo.
  • Thumbnail Image
    Item
    A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo
    (Springer Nature, 2019-06-11) Reissaus, Christopher A.; Piñeros, Annie R.; Twigg, Ashley N.; Orr, Kara S.; Conteh, Abass M.; Martinez, Michelle M.; Kamocka, Malgorzata M.; Day, Richard N.; Tersey, Sarah A.; Mirmira, Raghavendra G.; Dunn, Kenneth W.; Linnemann, Amelia K.; Pediatrics, School of Medicine
    The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche.