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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells
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Multivalent glibenclamide to generate islet specific imaging probes.

Andrej Babič1, Smaragda Lamprianou2, Laurent Vinet3

  • 1School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne, Geneva, Switzerland.

Biomaterials
|October 17, 2015
PubMed
Summary

Researchers developed novel multivalent probes targeting the sulphonylurea receptor subtype 1 (SUR1) for enhanced beta-cell imaging in diabetes mellitus. These glibenclamide-based probes show high affinity and specificity, offering a promising platform for advanced diagnostic imaging.

Keywords:
Beta-cellsDendrimersDiabetesImagingMultivalencySulphonylureas

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Area of Science:

  • Biomedical imaging
  • Drug discovery
  • Diabetes research

Background:

  • Monitoring diabetes mellitus progression is challenging for diagnostic imaging.
  • Current methods lack specificity for beta-cell imaging.

Purpose of the Study:

  • To develop novel multivalent probes for specific beta-cell imaging.
  • To target the sulphonylurea receptor subtype 1 (SUR1) using glibenclamide derivatives.

Main Methods:

  • Synthesized 11 glibenclamide derivatives and evaluated their SUR1 affinity in MIN6 cells.
  • Created multivalent glibenclamide-polyamidoamine (PAMAM) derivatives for imaging probe attachment.
  • Labeled probes with fluorochromes and assessed their performance in cellular and in vivo assays.

Main Results:

  • Developed multivalent probes with nanomolar affinity for SUR1, exceeding native glibenclamide.
  • Probes specifically labeled SUR1-expressing MIN6 cells, not HeLa or PANC-1 cells.
  • Demonstrated low cytotoxicity and successful in vivo labeling of beta-cells in mice and human islets.

Conclusions:

  • Multivalent glibenclamide derivatives offer a versatile platform for cell-specific imaging probes.
  • These probes can be adapted for multiple imaging modalities for diabetes diagnostics.
  • The developed probes show potential for improved monitoring of diabetes mellitus.