Qi Meirigeng, McFadden Brian, Valiente Luis, Omori Keiko, Bilbao Shiela, Juan Jemily, Rawson Jeffrey, Oancea Alina R, Scott Stephen, Nair Indu, Ferreri Kevin, Mullen Yoko, Dafoe Donald, Ei-Shahawy Mohamed, Kandeel Fouad, Al-Abdullah Ismail H
Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
Cell Transplant. 2015;24(9):1879-86. doi: 10.3727/096368914X683548. Epub 2014 Aug 5.
The aim of this study was to investigate the effects of elevated donor HbA1c levels (type 2 diabetes, T2D) on the islet yield and functionality postisolation. In this retrospective analysis, donors for islet isolations were classified into two groups: T2D group (HbA1c ≥ 6.5%, n = 18) and normal group (HbA1c < 6.5%, n = 308). Optimum pancreas digestion time (switch time) was significantly higher in the T2D group compared to the normal group (13.7 ± 1.2 vs. 11.7 ± 0.1 min, respectively, p = 0.005). Islet yields were significantly lower in the T2D group compared to the control (T2D vs. control): islet equivalent (IEQ)/g (prepurification 2,318 ± 195 vs. 3,713 ± 114, p = 0.003; postpurification 1,735 ± 175 vs. 2,663 ± 89, p = 0.013) and islet particle number (IPN)/g (prepurification, 2,519 ± 336 vs. 4,433 ± 143, p = 0.001; postpurification, 1,760 ± 229 vs. 2,715 ± 85, p = 0.007). Islets from T2D pancreata had significantly lower viability (T2D vs.
91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (ΔOCR) (T2D vs.
0.09 ± 0.01 and 0.21 ± 0.03 nmol O2 100 islets(-1) min(-1), p = 0.049). The islets isolated from T2D donor pancreata reversed diabetes in NOD-SCID mice in 9% (2/22) compared to islets from control donor pancreata, which reversed diabetes in 67% (175/260, p < 0.001). In conclusion, this study demonstrates that elevated HbA1c (≥ 6.5%) is associated with impairment of islet function and lower islet yield; however, these islets could not be suitable for clinical applications.
本研究旨在调查供体糖化血红蛋白A1c水平升高（2型糖尿病，T2D）对胰岛分离后产量和功能的影响。在这项回顾性分析中，胰岛分离的供体被分为两组：T2D组（糖化血红蛋白A1c≥6.5%，n = 18）和正常组（糖化血红蛋白A1c<6.5%，n = 308）。与正常组相比，T2D组的最佳胰腺消化时间（转换时间）显著更长（分别为13.7±1.2分钟和11.7±0.1分钟，p = 0.005）。与对照组相比，T2D组的胰岛产量显著更低（T2D组与对照组相比）：胰岛当量（IEQ）/克（纯化前2318±195与3713±114，p = 0.003；纯化后1735±175与2663±89，p = 0.013）以及胰岛颗粒数（IPN）/克（纯化前，2519±336与4433±143，p = 0.001；纯化后，1760±229与2715±85，p = 0.007）。来自T2D胰腺的胰岛活力显著更低（T2D组与对照组相比：91.9±1.6%与94.4±0.3%，p = 0.004）且氧消耗率（ΔOCR）降低（T2D组与对照组相比：0.09±0.01和0.21±0.03 nmol O2 100个胰岛⁻¹分钟⁻¹，p = 0.049）。与来自对照供体胰腺的胰岛相比，从T2D供体胰腺分离的胰岛在NOD - SCID小鼠中使糖尿病逆转的比例为9%（2/22），而对照供体胰腺的胰岛使糖尿病逆转的比例为67%（175/260，p < 0.001）。总之，本研究表明糖化血红蛋白A1c升高（≥6.5%）与胰岛功能受损和较低的胰岛产量相关；然而，这些胰岛可能不适用于临床应用。
