Noninvasive MRI of β-cell function using a Zn 2+ -responsive contrast agent

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 45; pp. 18400 - 18405
• Main Authors: Lubag, Angelo J. M., De Leon-Rodriguez, Luis M., Burgess, Shawn C., Sherry, A. Dean
• Format: Journal Article
• Language: English
• Published: 08.11.2011
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1109649108

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.