Whole-Body Evaluation of MIBG Tissue Extraction in a Mouse Model of Long-Lasting Type II Diabetes and Its Relationship with Norepinephrine Transport Protein Concentration
Whole-Body Evaluation of MIBG Tissue Extraction in a Mouse Model of Long-Lasting Type II Diabetes and Its Relationship with Norepinephrine Transport Protein Concentration
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DOI：
10.2967/jnumed.108.054361
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发表时间：
2008-10-01
影响因子：
9.3
通讯作者：
Sambuceti, Gianmario
中科院分区：
文献类型：
--
作者：
Kusmic, Claudia;Morbelli, Silvia;Sambuceti, Gianmario
I-123-间碘苄基胍 (MIBG) 的加速心脏冲洗（临床上用作糖尿病心脏神经病变的指标）归因于突触小泡去甲肾上腺素再摄取的减少。然而，加速洗脱常常与保留的早期示踪剂摄取形成对比，其重要性仍待确定。本研究的目的是在长期 II 型糖尿病小鼠模型中调查 MIBG 早期摄取和清除之间的不匹配是否是更广泛的自主神经系统紊乱的结果。方法：9只小鼠腹腔注射小剂量链脲佐菌素，连续5天。链脲佐菌素注射后 7 个月，通过心脏和肝脏时间-活动曲线以及膀胱中示踪剂积聚来评估 MIBG 动力学。将数据与 10 只假小鼠中获得的数据进行比较，并与用 H-3-地昔帕明饱和结合测定评估的去甲肾上腺素转运蛋白 (NET) 的心脏和肝组织表达相关。结果：在糖尿病小鼠中，心肌和肝脏 MIBG 保留在 2 小时时减少，并且与示踪剂洗脱增加和 NET 密度减少相关。心肌冲刷率与尿中 MIBG 排泄程度相关。结论：糖尿病患者早期摄取保留与 MIBG 加速清除相关的矛盾观察似乎可以用 NET 功能的普遍紊乱来解释，导致全身示踪剂从血液中去除减少，早期心肌摄取示踪剂可用性增加。
Accelerated cardiac washout of I-123-metaiodobenzylguanidine (MIBG), which is clinically used as an index of cardiac neuropathy in diabetes, is ascribed to decreased norepinephrine reuptake into synaptic vesicles. However, accelerated washout frequently contrasts with preserved early tracer uptake, whose significance remains undetermined. The aim of this study was to investigate in a mouse model of long-lasting type II diabetes whether the mismatch between MIBG early uptake and washout is the consequence of a more generalized disorder of the autonomic nervous system. Methods: Nine mice were given low doses of streptozotocin by intraperitoneal injection for 5 consecutive days. At 7 mo after streptozotocin, MIBG kinetics were evaluated by heart and liver time-activity curves and by tracer accumulation in the bladder. Data were compared with those obtained in 10 sham mice and correlated with the cardiac and hepatic tissue expression of norepinephrine transporter (NET) as assessed with a H-3-desipramine saturation binding assay. Results: In diabetic mice, myocardial and liver MIBG retention was reduced at 2 h and was associated with both increased tracer washout and reduced NET density. The rate of myocardial washout correlated with the degree of urinary MIBG excretion. Conclusion: The paradoxic observation of preserved early uptake associated with accelerated washout of MIBG in diabetes seems to be explained by a generalized disorder in NET function leading to reduced whole-body tracer removal from the blood and increased tracer availability for early myocardial uptake.