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

Elevation of postprandial glucose stimulates release of insulin from granules stored in pancreatic islet β-cells. We demonstrate here that divalent zinc ions coreleased with insulin from β-cells in response to high glucose are readily detected by MRI using the Zn²⁺-responsive T₁ agent, GdDOTA-diBPEN...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-11, Vol.108 (45), p.18400-18405
Main Authors: Lubag, Angelo J. M., De Leon-Rodriguez, Luis M., Burgess, Shawn C., Sherry, A. Dean
Format: Article
Language:English
Subjects:
Albumins
Animals
Biological Sciences
Contrast Media
Diabetes Mellitus, Experimental - physiopathology
Diabetes Mellitus, Type 1 - physiopathology
Dietary Fats - administration & dosage
Disease Models, Animal
Image contrast
Image enhancement
Imaging
Insulin
Islets of Langerhans - physiology
Magnetic Resonance Imaging - methods
Mice
Mice, Inbred C57BL
Pancreas
Sensors
Streptozocin
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Zinc
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Summary:Elevation of postprandial glucose stimulates release of insulin from granules stored in pancreatic islet β-cells. We demonstrate here that divalent zinc ions coreleased with insulin from β-cells in response to high glucose are readily detected by MRI using the Zn²⁺-responsive T₁ agent, GdDOTA-diBPEN. Image contrast was significantly enhanced in the mouse pancreas after injection of a bolus of glucose followed by a low dose of the Zn²⁺ sensor. Images of the pancreas were not enhanced by the agent in mice without addition of glucose to stimulate insulin release, nor were images enhanced in streptozotocin-treated mice with or without added glucose. These observations are consistent with MRI detection of Zn²⁺ released from β-cells only during glucose-stimulated insulin secretion. Images of mice fed a high-fat (60%) diet over a 12-wk period and subjected to this same imaging protocol showed a larger volume of contrast-enhanced pancreatic tissue, consistent with the expansion of pancreatic β-cell mass during fat accumulation and progression to type 2 diabetes. This MRI sensor offers the exciting potential for deep-tissue monitoring of β-cell function in vivo during development of type 2 diabetes or after implantation of islets in type I diabetic patients.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1109649108