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胰岛素受体底物-1(IRS-1)敲除小鼠作为胰岛素抵抗模型的器官特异性葡萄糖代谢¹⁸F-FDG 评价。

Evaluation of organ-specific glucose metabolism by ¹⁸F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance.

机构信息

Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

出版信息

Ann Nucl Med. 2011 Dec;25(10):755-61. doi: 10.1007/s12149-011-0522-y. Epub 2011 Aug 5.

DOI:10.1007/s12149-011-0522-y
PMID:21818569
Abstract

OBJECTIVE

Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [(18)F]-2-fluoro-2-deoxy-D: -glucose ([(18)F]-FDG).

METHODS

The biodistribution of [(18)F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [(18)F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [(18)F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter.

RESULTS

In the absence of insulin, the blood glucose concentrations of wild-type mice (132 ± 26 mg/dl) and IRS-1 knockout mice (134 ± 18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [(18)F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [(18)F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice.

CONCLUSION

Our results showed that IR significantly affected [(18)F]-FDG uptake in the heart in normal daily conditions. IR was associated with decreased [(18)F]-FDG uptake in the heart and was readily observed in the absence of insulin loading. [(18)F]-FDG-positron emission tomography (PET) could be a useful tool for evaluating insulin resistance in images by investigating tissue-specific differences in [(18)F]-FDG uptake.

摘要

目的

胰岛素抵抗(IR)是一种生理状态,即身体产生胰岛素,但没有产生足够的生物学效应。胰岛素抵抗通常没有症状,但与健康问题有关,是代谢综合征的一个因素。本研究的目的是使用 [(18)F]-2-氟-2-脱氧-D: -葡萄糖 ([(18)F]-FDG) 在正常日常条件下阐明器官特异性胰岛素抵抗。

方法

在胰岛素受体底物-1(IRS-1)敲除小鼠(骨骼肌胰岛素抵抗的动物模型)和接受或不接受胰岛素负荷的 C57BL/6J(野生型)小鼠中检查 [(18)F]-FDG 的生物分布。将 0.5 MBq 的 [(18)F]-FDG 注入尾静脉,立即给予无(对照队列)或 1.5 mU/g 体重的人胰岛素腹腔内注射作为胰岛素负荷试验。所有实验动物的血糖浓度在注射后 0、20、40 和 60 分钟进行评估。随后处死小鼠,收集组织评估 [(18)F]-FDG 生物分布。使用伽马计数器测量每个器官的放射性。

结果

在没有胰岛素的情况下,野生型小鼠(132±26mg/dl)和 IRS-1 敲除小鼠(134±18mg/dl)的血糖浓度没有显著差异。给予胰岛素后血糖浓度下降,20、40 和 60 分钟时野生型小鼠的浓度低于敲除小鼠。在心脏、腹部肌肉和股骨肌肉中,在野生型小鼠和 IRS-1 敲除小鼠之间确认了 [(18)F]-FDG 摄取的统计学显著差异。在有和没有胰岛素负荷的情况下,[(18)F]-FDG 在心脏、背部肌肉和腹部肌肉的摄取均显著增加。

结论

我们的结果表明,IR 显著影响正常日常条件下心脏中的 [(18)F]-FDG 摄取。IR 与心脏中 [(18)F]-FDG 摄取减少有关,在没有胰岛素负荷的情况下很容易观察到。[(18)F]-FDG-正电子发射断层扫描(PET)可以通过研究组织特异性 [(18)F]-FDG 摄取差异,成为评估胰岛素抵抗的有用工具。

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