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

ABSTRACT: Elevation of postprandial glucose stimulates release of insulin from granules stored in pancreatic islet ?-cells. We demonstrate here that divalent zinc ions coreleased with insulin from ?-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 ?-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 ?-cell mass during fat accumulation and progression to type 2 diabetes. This MRI sensor offers the exciting potential for deep-tissue monitoring of ?-cell function in vivo during development of type 2 diabetes or after implantation of islets in type I diabetic patients.

SUBMITTER: Lubag AJ 

PROVIDER: S-EPMC3215051 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature