Glial cell line-derived neurotrophic factor enhances human islet posttransplantation survival.
Glial cell line-derived neurotrophic factor enhances human islet posttransplantation survival.
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DOI：
10.1097/tp.0b013e31822bc95a
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发表时间：
2011-10-15
期刊：
影响因子：
6.2
通讯作者：
Srinivasan S
中科院分区：
文献类型：
--
作者：
Mwangi SM;Usta Y;Shahnavaz N;Joseph I;Avila J;Cano J;Chetty VK;Larsen CP;Sitaraman SV;Srinivasan S
开发移植前胰岛培养策略以保存或提高β细胞的活性，将消除对恢复1型糖尿病患者胰岛素独立性所需的大量胰岛的需求。我们研究了胶质细胞源性神经营养因子(GDNF)是否可以改善糖尿病小鼠的人胰岛存活和移植后功能。人胰岛在添加或不添加GDNF100 ng/ml的培养液中培养，通过分析β细胞的凋亡和葡萄糖刺激的胰岛素释放来评估胰岛的存活和功能。将2000个等效人胰岛移植到链脲佐菌素诱导的糖尿病裸小鼠肾包膜下，在添加或不添加GDNF的培养液中观察GDNF的体内作用。体外培养2-10天的人胰岛，与载体培养的胰岛相比，β-细胞死亡减少，Akt磷酸化增加，葡萄糖诱导的胰岛素分泌增加。在添加GDNF的培养液中预培养的人胰岛比在载体中培养的胰岛更能使糖尿病小鼠在移植后更长时间内恢复到正常血糖。我们的研究表明，GDNF对人胰岛存活有积极作用，可用于提高胰岛移植后的存活率。
Development of pre-transplantation islet culture strategies that preserve or enhance β-cell viability would eliminate the requirement for the large numbers of islets needed to restore insulin independence in type 1 diabetes patients. We investigated whether glial cell line-derived neurotrophic factor (GDNF) could improve human islet survival and post-transplantation function in diabetic mice. Human islets were cultured in medium supplemented with or without GDNF (100 ng/ml) and in vitro islet survival and function assessed by analyzing β-cell apoptosis and glucose stimulated insulin release. In vivo effects of GDNF were assessed in streptozotocin-induced diabetic nude mice transplanted under the kidney capsule with 2000 islet equivalents of human islets pre-cultured in medium supplemented with or without GDNF. In vitro, human islets cultured for 2–10 days in medium supplemented with GDNF showed lower β-cell death, increased Akt phosphorylation and higher glucose-induced insulin secretion than islets cultured in vehicle. Human islets pre-cultured in medium supplemented with GDNF restored more diabetic mice to normoglycemia and for a longer period after transplantation than islets cultured in vehicle. Our study shows that GDNF has beneficial effects on human islet survival and could be used to improve islet post-transplantation survival.