Blocking of Glucagonlike Peptide-1 Receptors in the Exocrine Pancreas Improves Specificity for β-Cells in a Mouse Model of Type 1 Diabetes Academic Article Article uri icon

Overview

MeSH Major

  • Antibodies, Neoplasm
  • Colorectal Neoplasms
  • Copper Radioisotopes
  • Cyclooctanes
  • Immunoconjugates
  • Positron-Emission Tomography
  • Radiopharmaceuticals

abstract

  • © 2019 by the Society of Nuclear Medicine and Molecular Imaging. The diabetes community has long desired an imaging agent to quantify the number of insulin-secreting β-cells, beyond just functional equivalents (insulin secretion), to help diagnose and monitor early stages of both type 1 and type 2 diabetes mellitus. Loss in the number of β-cells can be masked by a compensatory increase in function of the remaining cells. Since β-cells form only about 1% of the pancreas and decrease as the disease progresses, only a few imaging agents, such as exendin, have demonstrated clinical potential to detect a drop in the already scarce signal. However, clinical translation of imaging with exendin has been hampered by pancreatic uptake that is higher than expected in subjects with long-term diabetes who lack β-cells. Exendin binds glucagonlike peptide-1 receptor (GLP-1R), previously thought to be expressed only on β-cells, but recent studies report low levels of GLP-1R on exocrine cells, complicating β-cell mass quantification. Methods: Here, we used a GLP-1R knockout mouse model to demonstrate that exocrine binding of exendin is exclusively via GLP-1R (∼1,000/cell) and not any other receptor. We then used lipophilic Cy-7 exendin to selectively preblock exocrine GLP-1R in healthy and streptozotocin-induced diabetic mice. Results: Sufficient receptors remain on β-cells for subsequent labeling with a fluorescent- or 111In-exendin. Conclusion: Selective GLP-1R blocking, which improves contrast between healthy and diabetic pancreata and provides a potential avenue for achieving the long-standing goal of imaging β-cell mass in the clinic.

publication date

  • November 2019

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.2967/jnumed.118.224881

PubMed ID

  • 31076502

Additional Document Info

start page

  • 1635

end page

  • 1641

volume

  • 60

number

  • 11