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

AJM Lubag, LM De Leon-Rodriguez… - Proceedings of the …, 2011 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences