Brown Adipose Tissue: A Potential Site for Islet Transplantation

Brown Adipose Tissue: A Potential Site for Islet Transplantation
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DOI:
10.1097/tp.0000000000003322
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发表时间:
2020-05
期刊:
影响因子:
6.2
通讯作者:
Kang Xu;Raoying Xie;Xiaolin Lin;Jun-shuang Jia;Nan Zeng;Wangen Li;D. Xiao;Tao Du
Kang Xu;Raoying Xie;Xiaolin Lin;Jun-shuang Jia;Nan Zeng;Wangen Li;D. Xiao;Tao Du
中科院分区:
医学2区
文献类型:
--
作者:
Kang Xu;Raoying Xie;Xiaolin Lin;Jun-shuang Jia;Nan Zeng;Wangen Li;D. Xiao;Tao Du

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补充数字内容可在文本中找到。背景胰岛移植是治疗复杂糖尿病患者的一种很有前途的治疗方法。理想的移植部位,可以延长胰岛移植物的生存和减少所需的移植胰岛的数量仍然有待建立。方法.从红色荧光蛋白(RFP+)小鼠中分离供体胰岛,并移植到年龄匹配的糖尿病RFP−小鼠的肩胛间棕色脂肪组织(BAT)或单侧腹股沟白色脂肪组织中。监测小鼠血糖和体重,通过荧光成像、组织学检查和腹腔葡萄糖耐量试验(GTT)检测异位RFP+胰岛的活力和功能。结果BAT使移植胰岛的边缘数量(80个胰岛)在移植后的短期内在所有糖尿病受体小鼠中恢复血糖、胰岛素水平和GTT至正常值,并在实验结束时维持这些值1年。重要的是,在移植后的短期内,在BAT中观察到丰富的胰岛外和胰岛内新生血管,但在白色脂肪组织中没有,这使得异位胰岛保持典型的结构和形态,并有助于正常的GTT。此外,胰岛移植的BAT显示正常的结构和形态,没有明显的免疫细胞浸润,受体小鼠的血液中也显示正常的脂质水平。结论. BAT可显著提高异位胰岛移植后的存活率和生物学功能。此外,BAT的解剖位置适合于活检、切除和胰岛再移植,这强烈表明BAT是基础和临床研究中胰岛移植的潜在理想部位。
Supplemental Digital Content is available in the text. Background. Islet transplantation is a promising treatment in patients with complicated diabetes. The ideal transplant site that can extend islet graft survival and reduce the required number of engrafted islets remains to be established. Methods. Donor islets were isolated from red fluorescent protein (RFP+) mice and transplanted into interscapular brown adipose tissue (BAT) or unilateral inguinal white adipose tissue of age-matched diabetic RFP− mice. Blood glucose and body weight of the mice were monitored, and vitality and function of ectopic RFP+ islets were detected by fluorescence imaging, histological examination, and intraperitoneal glucose tolerance test (GTT). Results. BAT enabled the marginal number of grafted islets (80 islets) to restore blood glucose, insulin level, and GTT to normal values in all diabetic recipient mice in the short term after graft, and maintained these values for 1 year at the end of the experiment. Importantly, in the short term after transplantation, abundant extra- and intraislet neovasculatures were observed in BAT, but not in white adipose tissue, which allowed the ectopic islets to retain typical architecture and morphology and contributed to the normal GTT. Moreover, the islet-engrafted BAT displayed normal structure and morphology without significant immunocyte infiltration, and the recipient mice also showed normal lipid levels in the blood. Conclusions. BAT remarkably enhances the viability and biological function of the transplanted ectopic islets. Moreover, the anatomical location of BAT lends itself to biopsy, removal, and islet retransplantation, which strongly suggests the BAT as a potential desirable site for islet transplantation in basic and clinical research.