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Noninvasive MRI of β-cell function using a Zn2+-responsive contrast agent.

Angelo J M Lubag1, Luis M De Leon-Rodriguez, Shawn C Burgess

  • 1University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 26, 2011
PubMed
Summary

This study shows magnetic resonance imaging (MRI) can detect zinc ions released from pancreatic beta cells during glucose-stimulated insulin secretion. This novel MRI sensor may help monitor beta cell function in diabetes.

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Area of Science:

  • Biomedical Imaging
  • Endocrinology
  • Metabolic Diseases

Background:

  • Pancreatic beta cells release insulin in response to elevated blood glucose.
  • Divalent zinc ions are co-released with insulin and may serve as a biomarker.
  • Current methods for monitoring beta cell function are limited.

Purpose of the Study:

  • To develop and validate a novel MRI-based method for detecting zinc ion release from pancreatic beta cells.
  • To assess the potential of this method for monitoring beta cell function in vivo, particularly in the context of type 2 diabetes.

Main Methods:

  • Utilized a T(1)-weighted MRI agent (GdDOTA-diBPEN) responsive to divalent zinc ions (Zn2+).
  • Administered glucose bolus and the Zn2+ sensor to mice to stimulate insulin and zinc release.

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  • Compared MRI contrast enhancement in healthy, streptozotocin-treated, and high-fat diet-fed mice.

    • Main Results:

    • Significant MRI contrast enhancement was observed in the mouse pancreas after glucose administration, indicating Zn2+ release.
    • No contrast enhancement occurred in mice without glucose stimulation or in streptozotocin-treated mice.
    • Mice fed a high-fat diet showed increased contrast enhancement, correlating with expanded beta cell mass.

    Conclusions:

    • MRI detection of Zn2+ released from beta cells is feasible and specific to glucose-stimulated insulin secretion.
    • This MRI sensor has potential for non-invasive, deep-tissue monitoring of beta cell mass and function.
    • The method could aid in tracking type 2 diabetes progression and evaluating islet transplantation outcomes.