Noninvasive MRI of β-cell function using a Zn2+-responsive contrast agent
Noninvasive MRI of β-cell function using a Zn2+-responsive contrast agent
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DOI：
10.1073/pnas.1109649108
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发表时间：
2011-11-08
影响因子：
11.1
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
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作者：
Lubag, Angelo J. M.;De Leon-Rodriguez, Luis M.;Sherry, A. Dean
餐后葡萄糖升高刺激储存在胰岛β细胞中的颗粒释放胰岛素。我们在这里证明了二价锌离子在高葡萄糖反应下与胰岛素一起从β细胞释放，可以很容易地通过MRI检测到Zn2+反应性T-1剂GdDOTA-diBPEN。小鼠胰腺在注射葡萄糖后，再注射低剂量的Zn2+传感器，图像对比度显著增强。在没有添加葡萄糖以刺激胰岛素释放的小鼠中，该药物没有增强胰腺图像，在添加或不添加葡萄糖的链脲佐菌素处理的小鼠中，图像也没有增强。这些观察结果与仅在葡萄糖刺激胰岛素分泌时β细胞释放的Zn2+的MRI检测一致。喂食高脂肪（60%）饮食的小鼠在12周内的图像显示，对比度增强的胰腺组织体积更大，与脂肪积累和发展为2型糖尿病期间胰腺β细胞质量的扩大一致。这种MRI传感器在2型糖尿病发展过程中或1型糖尿病患者胰岛植入后体内β细胞功能的深层组织监测方面具有令人兴奋的潜力。
Elevation of postprandial glucose stimulates release of insulin from granules stored in pancreatic islet beta-cells. We demonstrate here that divalent zinc ions coreleased with insulin from beta-cells in response to high glucose are readily detected by MRI using the Zn2+-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 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 beta-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 beta-cell mass during fat accumulation and progression to type 2 diabetes. This MRI sensor offers the exciting potential for deep-tissue monitoring of beta-cell function in vivo during development of type 2 diabetes or after implantation of islets in type I diabetic patients.