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

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.
• 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.