Udayasankar J, Zraika S, Aston-Mourney K, Subramanian S L, Brooks-Worrell B M, Taborsky G J, Hull R L
Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108, USA.
Transplant Proc. 2013 Mar;45(2):574-9. doi: 10.1016/j.transproceed.2012.05.079. Epub 2012 Sep 25.
In human islet transplantation, insulin independence decreases over time. We previously showed that amyloid deposition following transplantation of islets from human islet amyloid polypeptide (hIAPP) transgenic mice resulted in ß-cell loss and that rosiglitazone treatment decreased islet amyloid deposition and preserved ß-cell area in the endogenous pancreas of hIAPP transgenic mice. Thus, we sought to determine if rosiglitazone treatment decreases islet amyloid deposition and the associated ß-cell loss after islet transplantation. Streptozocin-diabetic mice were transplanted with 100 islets from hIAPP transgenic (T) mice or nontransgenic (NT) littermates under the kidney capsule and received either rosiglitazone (R) in drinking water or plain drinking water (C). The resultant groups (NTC [n = 11], NTR [n = 9], TC [n = 14], and TR [n = 10]) were followed for 12 weeks after which the graft was removed and processed for histology. Amyloid was detected in nearly all T islet grafts (TC = 13/14, TR = 10/10) but not in NT grafts. Rosiglitazone did not alter amyloid deposition (% graft area occupied by amyloid; TC: 2.15 ± 0.7, TR: 1.72 ± 0.66; P = .86). % ß-cell/graft area was decreased in the TC grafts compared to NTC (56.2 ± 3.1 vs 73.8 ± 1.4; P < .0001) but was not different between TC and TR groups (56.2 ± 3.1 vs 61.0 ± 2.9; P = .34). Plasma glucose levels before and after transplantation did not differ between NTC and TC groups and rosiglitazone did not affect plasma glucose levels post-islet transplantation. Rosiglitazone did not decrease amyloid deposition in hIAPP transgenic islet grafts. Therefore, rosiglitazone treatment of recipients of amyloid forming islets may not improve transplantation outcomes.
在人类胰岛移植中，胰岛素非依赖状态会随时间推移而降低。我们之前的研究表明，移植来自人胰岛淀粉样多肽（hIAPP）转基因小鼠的胰岛后出现的淀粉样沉积会导致β细胞丢失，并且罗格列酮治疗可减少hIAPP转基因小鼠内源性胰腺中的胰岛淀粉样沉积并保留β细胞面积。因此，我们试图确定罗格列酮治疗是否能减少胰岛移植后的胰岛淀粉样沉积及相关的β细胞丢失。将链脲佐菌素诱导糖尿病的小鼠在肾被膜下移植100个来自hIAPP转基因（T）小鼠或同窝非转基因（NT）小鼠的胰岛，并给予饮用含罗格列酮（R）的水或普通饮用水（C）。对所得的几组小鼠（NTC [n = 11]、NTR [n = 9]、TC [n = 14]和TR [n = 10]）进行12周的跟踪观察，之后取出移植物并进行组织学处理。几乎在所有T组胰岛移植物中均检测到淀粉样物质（TC组为13/14，TR组为10/10），而在NT组移植物中未检测到。罗格列酮未改变淀粉样沉积（淀粉样物质所占移植物面积百分比；TC组：2.15±0.7，TR组：1.72±0.66；P = 0.86）。与NTC组相比，TC组移植物中β细胞/移植物面积百分比降低（56.2±3.1对73.8±1.4；P < 0.0001），但TC组和TR组之间无差异（56.2±3.1对61.0±2.9；P = 0.34）。NTC组和TC组移植前后的血浆葡萄糖水平无差异，且罗格列酮不影响胰岛移植后的血浆葡萄糖水平。罗格列酮未减少hIAPP转基因胰岛移植物中的淀粉样沉积。因此，对形成淀粉样物质的胰岛接受者进行罗格列酮治疗可能无法改善移植结局。
