Division of Digestive Diseases, Emory University, Atlanta, GA 30307, USA.
Transplantation. 2011 Oct 15;92(7):745-51. doi: 10.1097/TP.0b013e31822bc95a.
Development of pretransplantation 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 posttransplantation 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 precultured in medium supplemented with or without GDNF.
In vitro, human islets cultured for 2 to 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 precultured 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 posttransplantation survival.
开发移植前胰岛培养策略，既能保存又能增强β细胞活力，将消除 1 型糖尿病患者恢复胰岛素独立性所需的大量胰岛。我们研究胶质细胞源性神经营养因子（GDNF）是否能改善人胰岛在糖尿病小鼠中的存活和移植后功能。
用人胰岛在添加或不添加 GDNF（100ng/ml）的培养基中培养，通过分析β细胞凋亡和葡萄糖刺激胰岛素释放来评估体外胰岛的存活和功能。GDNF 的体内作用在链脲佐菌素诱导的糖尿病裸鼠中进行评估，这些裸鼠在肾包膜下移植了 2000 个胰岛当量的人胰岛，这些胰岛在添加或不添加 GDNF 的培养基中进行了预培养。
在体外，用人胰岛培养 2 至 10 天，在添加 GDNF 的培养基中培养的胰岛β细胞死亡较少，Akt 磷酸化增加，葡萄糖刺激胰岛素分泌增加，而在载体中培养的胰岛则减少。与人胰岛在添加 GDNF 的培养基中预培养相比，在载体中培养的胰岛在移植后恢复更多糖尿病小鼠的正常血糖水平，并维持更长时间。
我们的研究表明，GDNF 对人胰岛的存活有有益的影响，并可用于改善胰岛移植后的存活。
