College of Pharmacy and Gachon Institute Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon, Korea.
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-gu, Incheon, Korea.
Cell Transplant. 2020 Jan-Dec;29:963689720971245. doi: 10.1177/0963689720971245.
Islet transplantation has emerged as a promising treatment for type 1 diabetes mellitus. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, protects beta cells after islet transplantation by improving glycemic control through several mechanisms. In this study, we compared the effects of local pretreatment and systemic treatment with liraglutide on islet transplantation in a diabetic mouse model. Streptozotocin (STZ)-induced diabetic C57BL/6 mice were transplanted with syngeneic islets under the kidney capsule. Isolated islets were either locally treated with liraglutide before transplantation or mice were treated systemically by intraperitoneal injection after islet transplantation. Local pretreatment of islets with liraglutide was more effective in increasing body weight, decreasing hemoglobin A1c levels, and lowering blood glucose levels in STZ-diabetic mice transplanted with islets. Local pretreatment was also more effective in increasing insulin secretion and islet survival in STZ-diabetic mice. Histological analysis of the transplantation site revealed fewer apoptotic cells following local pretreatment compared with systemic injection of liraglutide. These findings indicate that liraglutide administered once locally before transplantation might have superior effects on islet preservation than systemic administration.
胰岛移植已成为 1 型糖尿病有前途的治疗方法。利拉鲁肽是一种胰高血糖素样肽-1（GLP-1）受体激动剂，通过多种机制改善血糖控制来保护胰岛移植后的β细胞。在这项研究中，我们比较了局部预处理和全身给予利拉鲁肽对糖尿病小鼠模型胰岛移植的影响。链脲佐菌素（STZ）诱导的糖尿病 C57BL/6 小鼠在肾包膜下移植同基因胰岛。在移植前，将分离的胰岛进行局部利拉鲁肽处理，或在胰岛移植后通过腹腔注射进行全身治疗。与全身注射利拉鲁肽相比，局部预处理胰岛更有效地增加了体重、降低了血红蛋白 A1c 水平和降低了 STZ 糖尿病小鼠的血糖水平。局部预处理还更有效地增加了胰岛素分泌和胰岛在 STZ 糖尿病小鼠中的存活。移植部位的组织学分析显示，与全身注射利拉鲁肽相比，局部预处理后凋亡细胞较少。这些发现表明，与全身给药相比，移植前局部给予一次利拉鲁肽可能对胰岛保存具有更好的效果。
