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 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.
University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Angelo J M
AJ
Lubag
Luis M
LM
De Leon-Rodriguez
Shawn C
SC
Burgess
A Dean
AD
Sherry
D000818:Animals; D003287:Contrast Media; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin; D015032:Zinc
D003287:Contrast Media; D004041:Dietary Fats; D013311:Streptozocin; D015032:Zinc