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

Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18400-5. doi: 10.1073/pnas.1109649108. Epub 2011 Oct 24.


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 Zn(2+)-responsive T(1) 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 Zn(2+) 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 Zn(2+) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Dietary Fats / administration & dosage
  • Disease Models, Animal
  • Islets of Langerhans / physiology*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred C57BL
  • Streptozocin
  • Zinc*


  • Contrast Media
  • Dietary Fats
  • Streptozocin
  • Zinc