Christiansen E, Kjems L L, Vølund A, Tibell A, Binder C, Madsbad S
Steno Diabetes Center, Gentofte, Denmark.
Am J Physiol. 1998 Apr;274(4):E716-25. doi: 10.1152/ajpendo.1998.274.4.E716.
After pancreas-kidney transplantation, it is difficult to obtain an accurate estimate of the insulin secretion of the pancreas graft, since several pitfalls are involved using peripheral C-peptide and/or insulin measurements in this determination. In this study, the individual kinetic parameters of C-peptide and then the rates of insulin secretion were estimated by two mathematical methods, the deconvolution method and the "combined model" during slow (oral glucose) and fast (intravenous glucagon) changes in insulin secretion in six successful pancreas-kidney transplant recipients with systemic delivery of insulin (Px), six nondiabetic kidney-transplant recipients with portal insulin secretion (Kx), six nondiabetic controls (NS), and six C-peptide-negative insulin-dependent diabetes mellitus patients (IDDM). Decreased C-peptide clearance and basal and poststimulatory hyperinsulinemia were found in both Px and Kx compared with NS (P < 0.05). Similar glucose responses were observed after intravenous glucagon in all groups, whereas the responses after oral glucose were 30% higher in Px and Kx than in NS (P < 0.05). During oral glucose and after intravenous glucagon, both mathematical methods resulted in significantly lower maximal and incremental insulin secretion rates (ISR) in Px than in Kx (P < 0.05). In contrast, calculations of incremental ISR in NS and Px induced by the two beta-cell stimuli were about the same but significantly higher in Kx than in NS (P < 0.05). These results differed markedly from those obtained using peripheral measurements of insulin and C-peptide alone. In conclusion, when C-peptide clearance and insulin metabolism change, such as in pancreas-kidney transplant recipients, accurate evaluation of insulin secretion from the graft can be obtained only by using individual kinetics of the peptides before calculating the ISR. This study also clearly demonstrates that insulin secretion after pancreas transplantation is still defective.
胰腺 - 肾脏移植后，很难准确评估胰腺移植物的胰岛素分泌情况，因为在通过外周C肽和/或胰岛素测量来进行此项测定时存在一些缺陷。在本研究中，采用两种数学方法，即去卷积法和“联合模型”，对6例成功进行胰腺 - 肾脏移植且胰岛素经全身递送的受者（Px组）、6例非糖尿病性肾脏移植且胰岛素经门静脉分泌的受者（Kx组）、6例非糖尿病对照者（NS组）以及6例C肽阴性的胰岛素依赖型糖尿病患者（IDDM组）在胰岛素分泌缓慢（口服葡萄糖）和快速（静脉注射胰高血糖素）变化期间的C肽个体动力学参数以及胰岛素分泌速率进行了评估。与NS组相比，Px组和Kx组均出现C肽清除率降低以及基础和刺激后高胰岛素血症（P < 0.05）。所有组静脉注射胰高血糖素后的葡萄糖反应相似，而Px组和Kx组口服葡萄糖后的反应比NS组高30%（P < 0.05）。在口服葡萄糖期间以及静脉注射胰高血糖素后，两种数学方法均显示Px组的最大和增量胰岛素分泌率（ISR）显著低于Kx组（P < 0.05）。相比之下，两种β细胞刺激诱导的NS组和Px组的增量ISR计算结果大致相同，但Kx组显著高于NS组（P < 0.05）。这些结果与仅使用外周胰岛素和C肽测量所获得的结果明显不同。总之，当C肽清除率和胰岛素代谢发生变化时，如在胰腺 - 肾脏移植受者中，只有在计算ISR之前使用肽的个体动力学才能准确评估移植物的胰岛素分泌。本研究还清楚地表明，胰腺移植后的胰岛素分泌仍然存在缺陷。
