胃黏膜下层胰岛移植物的生存率与功能的实验研究

目的 探讨胃黏膜下层胰岛移植的可行性.方法 应用雄性Wistar-Furth大鼠,STZ介导糖尿病大鼠模型.同种同基因大鼠体外胰岛分离纯化,分别移植进入糖尿病大鼠胃黏膜下层或肾被膜下,移植后不同时间段评估移植物生存率与代谢功能.结果 移植后早期移植胰岛被有效确认,并迅速分泌胰岛素逆转大鼠高血糖状况,糖耐受功能良好,与肾被膜下移植组比较,差异无显著意义.移植后4周,胃黏膜下移植组胰岛移植物胰岛素分泌功能逐渐丧失.结论 胃黏膜下胰岛移植技术具有良好的开发前景,如何提高其远期效果有待进一步考证.     

胃黏膜下层胰岛移植物的生存率与功能的实验研究

目的 探讨胃黏膜下层胰岛移植的可行性.方法 应用雄性Wistar-Furth大鼠,STZ介导糖尿病大鼠模型.同种同基因大鼠体外胰岛分离纯化,分别移植进入糖尿病大鼠胃黏膜下层或肾被膜下,移植后不同时间段评估移植物生存率与代谢功能.结果 移植后早期移植胰岛被有效确认,并迅速分泌胰岛素逆转大鼠高血糖状况,糖耐受功能良好,与肾被膜下移植组比较,差异无显著意义.移植后4周,胃黏膜下移植组胰岛移植物胰岛素分泌功能逐渐丧失.结论 胃黏膜下胰岛移植技术具有良好的开发前景,如何提高其远期效果有待进一步考证.     

小鼠腹股沟皮下脂肪组织与肾被膜部位移植胰岛降血糖功能的比较

目的比较腹股沟皮下白色脂肪组织与肾被膜下移植胰岛治疗小鼠1型糖尿病的效果。方法将1型糖尿病模型小鼠分为白色脂肪组(10只)和肾被膜组(10只)接受胰岛移植。胰岛分离和纯化后,分别移植到腹股沟皮下白色脂肪组织和肾被膜下位点。术后持续监测两组受体小鼠的随机血糖水平、糖耐量功能,移植后100 d摘取两组存活受体小鼠的胰岛移植物进行组织病理学检查。结果白色脂肪组有6只受体小鼠的血糖在移植后1个月恢复正常水平,其余4只受体小鼠一直维持着高血糖状态,陆续在监测结束前发生死亡;肾被膜组10只受体小鼠的血糖均在移植后10 d内恢复正常。白色脂肪组和肾被膜组受体小鼠的胰岛移植物均能降低血糖水平,但白色脂肪组胰岛移植物需要较长的时间方能发挥降血糖功能。肾被膜组小鼠的糖耐量功能优于白色脂肪组小鼠(P0.05)。组织病理学检查显示白色脂肪组和肾被膜组胰岛移植物的胰岛素表达均正常。结论腹股沟皮下白色脂肪组织部位移植胰岛能有效地发挥调控血糖变化的功能,尽管其降血糖功能稍弱于肾被膜下部位,但具有贴近理想胰岛移植位点的众多优势,是一个值得研究的胰岛移植替代部位。     

激活型Akt1转染大鼠胰岛联合免疫抑制剂在异种胰岛移植中的应用

目的 探讨腺病毒载体介导激活性Akt1基因(Adv-CA-Akt1)转染大鼠胰岛对异种移植胰岛功能和存活的影响.方法 以BALB/C糖尿病小鼠为受体,分离纯化雄性Wistar大鼠胰岛,体外培养,Adv-CA-Akt1转染后异种胰岛移植.受体小鼠分3组,实验组:Adv-CA-Akt1转染的大鼠胰岛体外培养24 h,小鼠肾被膜下移植,并口服环孢素A(CsA)30 mg·kg-1·d-1;CsA组:未转染胰岛移植,同剂量环孢素口服;对照组:单纯胰岛移植.每只接受300胰岛当量(IEQs)移植.检测术后血糖,移植物存活时间及组织病理学.结果 实验组和CsA组术后2 d血糖即降至正常,胰岛功能存活时间分别为(21.0±3.65)d和(9.0±2.54)d,而对照组血糖短暂下降后再次升高,胰岛功能存活时间(4.2±2.6)d.实验组小鼠生存时间为(31.0±5.67)d比CsA组(17.0±3.35)d和对照组(10.0±1.52)d明显延长,三组比较差异有统计学意义(P<0.05);胰岛素免疫组化染色实验组.肾被膜下见较多有功能胰岛细胞团,而CsA组和对照组胰岛素染色阳性细胞数减少.结论 Adv-CA-Akt1转染大鼠胰岛联合应用免疫抑制剂,可提高胰岛功能,延长异种胰岛移植物存活时间.     

腺病毒介导rhbFGF基因转染胰岛后促进小鼠被膜下移植的研究

目的 探讨重组人碱性成纤维生长因子（rhbFGF）基因导入胰岛细胞团后经肾被膜下移植,对移植物微血管重建的影响。方法 采用携带rhbFGF-flag-GFP基因的腺病毒载体体外转染培养的胰岛细胞团,再移植至同系糖尿病小鼠的肾被膜下,术后30 d内观察糖尿病治疗情况,通过术后14 d糖耐量试验和HE、免疫组化等观察胰岛功能和移植物的微血管重建结果。结果 感染复数（MOI）为100的rhbFGF基因转染后胰岛与未处理的胰岛在体外培养60 h后活性无统计学差异（P=0.75）;移植200 IEQ转基因胰岛至体内14 d后,胰岛功能良好,微血管重建增加,优于单独400 IEQ胰岛移植组。结论 rhbFGF基因导入胰岛移植有助于提高胰岛的功能,促进移植物微血管重建,并可减少胰岛移植量。     

激活型Akt1转染大鼠胰岛对移植物凋亡和再血管化的影响

目的 探讨腺病毒介导激活型蛋白激酶B(Akt1)基因(Adv-CA-Akt1)转染大鼠胰岛对同种糖尿病大鼠胰岛移植物凋亡和再血管化的影响.方法 分离纯化Wistar大鼠胰岛,转染Adv-CA-Akt1.36只糖尿病Wistar大鼠完全随机均分为3组: Adv-CA-Akt1组(Adv-CA-Akt1转染的胰岛移植); Adv-LacZ组(Adv-LacZ转染的胰岛移植); 未转染组(单纯胰岛移植).术后每日测血糖,隔日测血清胰岛素浓度,术后10 d行静脉糖耐量试验(IVGTT)观察胰岛功能; HE染色和胰岛素免疫组化检测胰岛功能,细胞凋亡原位检测胰岛凋亡,CD31免疫组化计数微血管密度(MVD).结果 Adv-CA-Akt1组大鼠血糖术后2 d恢复正常,Adv-LacZ组和未转染组血糖虽下降但仍高于正常; Adv-CA-Akt1组术后各时相血清胰岛素水平明显高于其他2组(P＜0.05).IVGTT示Adv-CA-Akt1组血糖下降较快,60 min恢复至空腹水平; 另2组下降慢,60 min仍未恢复至空腹水平.术后3 d,Adv-CA-Akt1组肾被膜下存活胰岛细胞数量多,胰岛素免疫组化证明为有功能的胰岛.Adv-CA-Akt1组胰岛凋亡率比Adv-LacZ组和未转染组降低约25%; 术后12 d,Adv-CA-Akt1组MVD比Adv-LacZ组及未转染组明显增高(P＜0.05).结论 激活型Akt1转染大鼠胰岛能够抑制胰岛细胞凋亡,提高胰岛β细胞功能,促进移植物早期再血管化.     

新生猪Sertoli细胞与大鼠胰岛细胞联合移植延长大鼠移植胰岛的存活时间

目的 探讨新生猪Sertoli细胞(NPSCs)与大鼠胰岛细胞联合移植对延长大鼠同种异体胰岛移植物存活时间的作用及其主要的机制.方法 将糖尿病Wistar大鼠随机分为3组.(1)单纯移植组(n=6):单纯移植1500个胰岛当量(IEQ)的SD大鼠胰岛细胞至糖尿病大鼠的左肾包膜下;(2)分侧移植组(n=4):将1500个IEQ的SD大鼠胰岛细胞移植到糖尿病大鼠的左肾包膜下,同时将1×10~7个NPSCs移植到糖尿病大鼠的右肾包膜下;(3)混合移植组(n=6):将1500个IEQ的SD大鼠胰岛细胞和1×10~7个NPSCs混合移植到糖尿病大鼠的左肾包膜下.移植后每天监测各组的血糖水平,以了解移植物的存活时间;移植后发生排斥反应时获取移植物标本,行HE和免疫组织化学染色,观察移植物中CD3~+T淋巴细胞浸润情况及细胞凋亡调控基因(Bcl-2)和血红素氧合酶1(HO-1)基因的表达水平.结果 单纯移植组、分侧移植组和混合移植组胰岛移植物存活时间分别为(5.7±1.0)d、(5.3±0.5)d和(16.3±1.4)d,混合移植组存活时间较其他两组显著延长(P<0.05).单纯移植组移植区可见大量淋巴细胞浸润,主要为CD3+T淋巴细胞;混合移植组移植区Bcl-2基因呈高表达;各组移植区HO-1基因均有表达,差异不明显.结论 NPSCs与大鼠胰岛细胞联合移植可以延长大鼠同种异体胰岛移植物的存活时间,其机制可能与NPSCs抑制移植物淋巴细胞浸润、促进Bcl-2基因高表达的局部免疫调节作用有关.     

同种异体胰岛及胰腺干细胞来源的胰岛样结构序贯移植治疗糖尿病

目的 观察同种异体大鼠胰岛及胰腺干细胞来源的胰岛样结构序贯移植在糖尿病治疗中的作用.方法 分离胰腺组织获得胰岛及胰腺导管上皮细胞,将具有干细胞潜能的胰腺导管上皮细胞在体外培养27d.将新鲜分离的胰岛(200±50)个及诱导分化2周的胰腺干细胞来源的胰岛样结构(2×106)个序贯移植到糖尿病大鼠的肾被膜下观察大鼠的血糖及生存情况.结果 将胰岛及胰腺干细胞来源的胰岛样结构序贯移植到同一糖尿病大鼠3周后血糖仍在5 mmol/L水平,对照组血糖无明显下降.结论 胰腺干细胞可诱导分化为分泌胰岛素的胰岛样结构,胰岛及胰腺干细胞来源的胰岛样结构序贯移植对大鼠糖尿病有治疗作用.     

肝星状细胞对同种异体胰岛移植物的保护作用

目的 研究小鼠肝星状细胞对同种异体胰岛移植物的保护作用.方法 将糖尿病小鼠随机分为三组,分别为糖尿病组、单纯胰岛移植组及与肝星状细胞共同移植组.单纯移植组于肾被膜下移植入同种异体胰岛300个;共同移植组移植入肝星状细胞(3×105个)与同种异体胰岛(300个)混合物.分别于移植术后监测受体小鼠血糖值及正常血糖维持时间;血糖正常一周后移植组及糖尿病组小鼠分别采血检测血清中TGF-β,TNF-α,IL-1β,IFN-γ的含量,同时取出移植物进行免疫组织化学检测.结果 术后共同移植组受体正常血糖维持时间为(23.75±8.96)d,单纯胰岛移植组受体正常血糖维持时间为(11.9±6.92)d,差异有统计学意义(P<0.05);三组受体血清中TNF-α、IL-1β、IFN-γ含量差异无统计学意义(P>0.05),共同移植组受体血清中TGF-β含量为(2292.31±5.87)pg/ml,单纯移植组为(1246.55±38.91)pg/ml,两组比较差异有统计学意义(P<0.05);病理学结果显示共同移植组胰岛素表达量大,并且在移植物周围有生物包膜形成.结论 在同种异体移植模型中,肝星状细胞可能通过高分泌TGF-β、局部形成包囊等方式保护胰岛移植物并延长其存活时间.     

脂肪间充质干细胞与胰岛联合移植对术后免疫状态及移植效果的影响

目的研究同系脂肪间充质干细胞(AMSC)与同种异体胰岛联合移植对胰岛移植术后免疫状态及移植效果的影响。 方法选择Lewis大鼠建立链脲佐菌素诱导的糖尿病大鼠模型作为胰岛移植受体,AMSC＋胰岛移植组经左肾包膜下联合移植Lewis大鼠AMSC及Wistar大鼠胰岛,单纯胰岛移植组经左肾包膜下单独移植Wistar大鼠胰岛,单纯AMSC移植组经左肾包膜下单独移植Lewis大鼠AMSC,阳性对照组为未进行移植的Lewis糖尿病大鼠,阴性对照组为正常Lewis大鼠。ELISA法检测血清细胞因子IFN-γ、IL-2、IL-4和IL-10浓度,流式细胞技术检测外周血CD4^＋、CD8^＋ T细胞比例,HE染色观察移植胰岛淋巴细胞浸润情况,观察血糖、胰岛素水平及胰岛移植物存活时间。采用单因素方差分析比较5组大鼠外周血淋巴细胞亚群比例和血清细胞因子水平,采用LSD法进行组间两两比较;血糖及血清胰岛素变化采用重复测量资料方差分析;采用独立样本t检验比较AMSC＋胰岛移植组与单纯胰岛移植组胰岛移植物淋巴细胞计数。采用Kaplan-Meier法绘制AMSC＋胰岛移植组与单纯胰岛移植组胰岛移植物生存曲线,并采用log-rank检验进行比较。P<0.05为差异有统计学意义。 结果AMSC＋胰岛移植组胰岛移植物平均生存时间为(26.8±3.0) d,长于单纯胰岛移植组的(19.0±1.3) d,两组大鼠胰岛移植物生存曲线差异有统计学意义(χ²＝4.494,P<0.05)。胰岛移植后各时间点,AMSC＋胰岛移植组大鼠移植后血糖和胰岛素水平均优于单纯胰岛移植组(P均<0.05)。胰岛移植前,5组大鼠外周血CD4^＋、CD8^＋ T细胞比例以及细胞因子IFN-γ、IL-2、IL-4和IL-10差异均无统计学意义(F＝0.425、0.476、0.256、0.418、0.281和0.313,P均>0.05)。胰岛移植后第7、14、28天,AMSC＋胰岛移植组大鼠外周血CD4^＋、CD8^＋T细胞比例均低于单纯胰岛移植组(P均<0.05),血清IFN-γ和IL-2浓度均低于单纯胰岛移植组(P均<0.05),IL-4和IL-10浓度均高于单纯胰岛移植组(P均<0.05)。胰岛移植第7天,AMSC＋胰岛移植组胰岛移植物平均淋巴细胞计数为(142±21)个/mm²,低于单纯胰岛移植组的(311±36)个/mm²(t＝8.245,P<0.05)。 结论与胰岛联合移植的AMSC能够提高胰岛移植的效果,可调节糖尿病大鼠体内IFN-γ、IL-2、IL-4和IL-10表达及抑制同种异体胰岛刺激的T细胞增殖,减轻胰岛移植物的免疫损伤。     

Long‐term engraftment and function of transplanted pancreatic islets in vascularized segments of small intestine

This study evaluated the potential of vascularized small intestinal segments for pancreatic islet transplantation. Islets isolated from Lewis rats were transplanted into diabetic syngeneic recipients. Segments of small intestine were prepared by denudation of the mucosal layer prior to implantation of pancreatic islets into the segments. Animal groups were established to determine engraftment, survival and function of islets transplanted into either intestinal segments or portal vein over up to 60 days. We found transplantation of functionally intact pancreatic islets into small intestinal segments was well tolerated. Transplanted islets were rapidly engrafted in intestinal segments as demonstrated vascularization and expression of insulin and glucagon throughout the 60‐day duration of the studies. Transplantation of islets restored euglycemia in diabetic rats, which was similar to animals receiving islets intraportally. Moreover, animals treated with islet transplants showed normal responses to glucose challenges. Removal of graft‐bearing intestinal segments led to recurrence of hyperglycemia indicating that transplanted islets were responsible for improved outcomes. Therefore, we concluded that vascularized intestinal segments supported reorganization, survival and function of transplanted islets with therapeutic efficacy in streptozotocin‐treated diabetic rats. The approach described here will be appropriate for studying islet biogenesis, reorganization and function, including for cell therapy applications.     

Morphological and functional studies on submucosal islet transplants in normal and diabetic hamsters

The long-term outcome of human islet allotransplantation is poor, and it remains to be seen if the Edmonton Protocol will make a positive impact upon the extension of posttransplant islet function. Hence, establishing an implantation site capable of sustaining islet allografts for a prolonged duration needs to be explored. In this study we investigated the submucosal space of the duodenum in Syrian golden hamsters. Following transplantation of more than 800 islets into streptozotocin (STZ)-induced diabetic hamsters, basal nonfasted blood glucose levels decreased from 403 +/- 14 to 143 +/- 10 mg/dl within 5 weeks posttransplantation. In these animals, in vivo islet function, as determined by intravenous glucose tolerance test (IVGTT), was similar to nondiabetic controls (K values: 1.16 +/- 0.12 vs. 0.95 +/- 0.06, respectively) and was significantly greater than diabetic controls (K value: 0.47 +/- 0.07). Islets transplanted into the submucosal space become richly vascularized within 2 weeks, and there is minimal host inflammatory infiltrate. The beta-cells of the graft remain well granulated with insulin for at least 129 days. We conclude that the submucosal space is an effective engraftment site for islets that warrants further development in a large-animal model.     

Downregulation of apoptosis-related genes in keloid tissues

BACKGROUND: The induction of immunological tolerance by orthotopic liver transplantation (OLT) is donor-specific. Moreover, after the acceptance of a liver, other organs are not rejected. The aim of this study is to clarify characteristics of the prolonged islet survival as a result of immunological tolerance which was induced following simultaneous OLT. MATERIALS AND METHODS: About 2000 islets were isolated from F344 rats. OLT was performed from F344 rats to diabetic LEW rats. Then the islets were transplanted into the transplanted F344 livers of diabetic LEW rats. Survival of the pancreatic islet allografts and deposits of IgM and IgG in the transplanted liver and islets were investigated. RESULTS: Survival time in the group with OLT (mean survival time: 46.4 +/- 38.2 days) was significantly longer than that without OLT (mean survival time: 8.1 +/- 0.8 days) (P < 0.01). Amount of serum antibody against donor lymphocytes was slightly higher in the group without OLT, and was very high in the group with OLT. Histologically, severe lymphocytic infiltration was observed in the Glisson's sheaths in the group with OLT. Islets were lodged, without lymphocytes inside, in small branches of the portal vein 7 days after transplantation. Immunohistologically, IgM and IgG deposits were found in the Glisson's sheaths and along sinusoids; however, they were not found in the islets. CONCLUSIONS: Induction of immunological tolerance and long-term survival of islets are possible by simultaneous OLT. The mechanism of this tolerance could be the host's selection of the liver as a target of preferred immunological attack.     

Allotransplantation of rat islets into the cisterna magna of streptozotocin-induced diabetic rats.

Islets were isolated from the pancreata of Sprague-Dawley rats and transplanted into streptozotocin-induced diabetic outbred Wistar rats. The effect of transplantation of islets into the cisterna magna on the diabetic state of the recipients was compared with that of the conventional transplantation of islets into liver via the portal vein. After successful intraportal (IP) transplantation, rejection took place between days 7 and 15 in all diabetic recipients. All of the eleven rats surviving after stereotaxic implantation of islets into the cisterna magna returned to normoglycemia within 7 days after transplantation. Nine of the recipients with intra-cisterna magna (IM) islet allografts were still normoglycemic at 210 days after transplantation. The glucose disappearance rate of the IM transplant rats was slower than that of the IP transplant rats, and blood glucose returned to the normal basal level within 5 hr following glucose administration. Although the insulin levels were almost undetectable in cerebrospinal fluid before IM transplantation, the insulin levels were markedly increased after IM transplantation and twice as great in CSF than blood. Thus, these findings indicate that the cisterna magna can serve as an immunologically privileged site for implantation of allogeneic pancreatic islets, and islets in CSF can regulate and maintain normal glucose homeostasis via secretion of insulin across the blood-brain barrier.     

Endoscopic Gastric Submucosal Transplantation of Islets (ENDO-STI): Technique and Initial Results in Diabetic Pigs

The results of transplantation of human donor islets into the portal vein (PV) in patients with diabetes are encouraging. However, there are complications, for example, hemorrhage, thrombosis and an immediate loss of islets through the 'instant blood-mediated inflammatory reaction' (IBMIR). The gastric submucosal space (GSMS) offers potential advantages. Islets were isolated from adult pigs. Recipient pigs were made diabetic by streptozotocin. Donor islets were injected into the GSMS through a laparotomy (Group 1A, n = 4) or endoscopically (Group 1B, n = 8) or into the PV through a laparotomy (Group 2, n = 3). The pigs were followed for a maximum of 28 days. Monitoring of C-peptide in Group 1 indicated that there was minimal immediate loss of islets whereas in Group 2 there was considerable loss from IBMIR. In Group 1, there were significant reductions in mean blood glucose and mean exogenous insulin requirement between pretransplantation and 20 days posttransplantation. In Group 2, there was no significant reduction in either parameter. Insulin-positive cells were seen in the GSMS in Group 1, but not in the liver in Group 2. Endoscopic gastric submucosal transplantation of islets (ENDO-STI) offers a minimally invasive and quick approach to islet transplantation, avoids IBMIR and warrants further exploration.     

Transplantation of fetal rat islets into the cerebral ventricles of alloxan-diabetic rats. Amelioration of diabetes by syngeneic but not allogeneic islets

Syngeneic fetal rat islets were isolated and transplanted into alloxan-diabetic inbred male Lewis rats. The effect of transplantation of islets into the cerebral ventricles on the diabetic state of the recipients was compared with that of the conventional transplantation of islets homeotypically into the liver via the portal vein. Fourteen of fourteen rats surviving after stereotaxic implantation of islets into the ventricles returned to normoglycemia; normoglycemia has been maintained for up to 34 wk. Glucose tolerance tests revealed an improved, although not completely normalized, pattern. Histologic examination of the brains of these recipients revealed clusters of intact islets in the ventricle. These data provided a physiologic basis for further investigation of the immunologically privileged nature of the intraventricular space as a site for implantation of allogeneic pancreatic islets. Islets from Wistar-Furth rats (major histocompatibility difference) or Fischer 344 rats (minor histocompatibility difference) were transplanted into the ventricles of alloxan-diabetic Lewis rats. There were only small and unsustained changes in body weight and blood and urine glucose of any of the rats receiving the allogeneic islets. Histologic examination of the ventricles of these rats 3 wk after transplantation revealed only glial scar tissue. These data suggest that the cerebral ventricles cannot serve as a privileged site for islet transplantation, at least using the type of islet preparation employed in these experiments.     

转染人VEGF165基因对大鼠胰岛移植物再血管化及生物学功能的影响

目的探讨转染人血管内皮生长因子（VEGF）基因对大鼠胰岛移植物再血管化和生物学功能的影响。方法实验分二步进行，首先构建携带人血管内皮生长因子165（hVEGF165）基因的重组腺病毒载体AdhVEGF165，用其按病毒／细胞的感染倍数（MOI）分别为10、100、500的比例在体外转染新鲜分离、纯化的近交系Lewis大鼠胰岛，检测体外培养的胰岛表达hVEGF165基因的情况；然后按MOI为10的比例在体外用AdhVEGF165转染Lweis大鼠胰岛，再经门静脉注射至近交系Lewis大鼠的肝脏内（VEGF组），并设不含hVEGF165基因的空载体转染对照组（GFP组）和磷酸盐缓冲液处理对照组（PBS液组），术后测定受鼠的血糖变化，进行静脉糖耐量试验（IVGTT），并观察受鼠肝脏中移植胰岛的组织学变化。结果体外转染hVEGF165基因的大鼠胰岛分泌至细胞外的hVEGF165的浓度显著高于未转染者（P〈0．01）。糖尿病大鼠移植转染hVEGF165基因的胰岛后，静脉注射葡萄糖后40、60、120min时的血糖水平显著低于GFP组和PBS液组（P〈0．05）；40min时体循环中胰岛素的浓度，VEGF组显著高于GFP组和PBS液组（P〈0．05）；VEGF组移植胰岛内CD34和胰岛素免疫组化染色的强度均高于GFP组和PBS液组。结论转染hVEGF165基因对胰岛移植物的再血管化和生物学功能有促进作用。     

Gastric submucosal alleviated pro-inflammation cytokines mediated initial dysfunction of islets allografts

BackgroundThe liver and renal capsule are the most common site for experimental pancreatic islet transplantation, but it is not optimal. Gastric submucosa space may be an ideal site for islet transplantation; however, whether pro-inflammation factors mediated islet dysfunction could be avoided or alleviated is still unclear.MethodsIslets of Sprague Dawley (SD) rat were transplanted into the streptozotocin-induced diabetic SD rats. Transplantation sites included gastric submucosa (GS), intraportal vein (PV) and kidney capsule (KC), and the efficiency of glycemic control and site-specific differences of islet grafts were compared.ResultsWith limited number of islets (800 IEQ) transplanted, improvement of recipient glycometabolism was superior in the GS group. When transplanted with 1200 IEQ islets, the survival of islet grafts were significantly prolonged in the GS group (25.87 ± 4.08 days, compared to 15.97 ± 0.83 days and 17.33 ± 1.41 days in PV and KC groups, respectively, P < .05). Compared with the PV group, the levels of IL-1β and TNF-α were significantly depressed in GS group after 12 h transplantation (15.5 ± 0.70 pg/mL and 13.28 ± 2.80 pg/mL vs. 262.26 ± 53.37 pg/mL and 138.51 ± 39.58 pg/mL, P < .05).ConclusionsGastric submucosal would be a potential ideal site for islet transplantation in rat. Gastric submucosal might alleviate the early islet dysfunction triggered by the IL-1β and TNF-α, and which requires a low number of transplanted islets and have a good glycemic control in return.