Teuscher A U, Kendall D M, Smets Y F, Leone J P, Sutherland D E, Robertson R P
Pacific Northwest Research Foundation, Seattle, Washington 98122, USA.
Diabetes. 1998 Mar;47(3):324-30. doi: 10.2337/diabetes.47.3.324.
Islet autotransplantation for treatment of chronic painful pancreatitis in nondiabetic patients reliably establishes normoglycemia and phasic insulin secretion and can achieve prolonged insulin independence. Whether functional transplanted beta-cell reserve is normal after intrahepatic islet transplantation is not known, nor is it known whether conventional measures of insulin secretion accurately reflect the functional beta-cell mass. To determine insulin secretory reserve after islet transplant, we performed studies of glucose potentiation of arginine-induced insulin secretion (GPAIS) in eight recipients of intrahepatic islet autotransplants. All eight subjects (and matched, healthy controls) were studied cross-sectionally 49 +/- 12 months posttransplant, and four subjects were studied pre- and posttransplant. Subjects had received a mean +/- SE of 479,000 +/- 79,000 islets, and all were insulin independent and normoglycemic at the time of study. Acute insulin responses to arginine, glucose, and GPAIS were significantly reduced after islet transplantation in both study groups. Importantly, the magnitudes of these three responses were highly correlated to the mass of islets transplanted (response to glucose: r = 0.84, P < 0.01; response to arginine: r = 0.69, P < 0.05; response to GPAIS = 0.81, P < 0.01). Data from hemipancreatectomized and normal control subjects generally agreed with the regression lines. These findings demonstrate that despite normoglycemia and insulin independence, recipients of intrahepatic islet transplantation have significantly reduced functional beta-secretory reserve and that after islet transplantation, functional beta-cell mass can be estimated by measurements of glucose and arginine-induced insulin responses. Thus, these measurements can be used to estimate the mass and functional capacity of islets surviving intrahepatic transplantation in humans.
胰岛自体移植用于治疗非糖尿病患者的慢性疼痛性胰腺炎，可可靠地建立正常血糖和阶段性胰岛素分泌，并可实现长期胰岛素非依赖。肝内胰岛移植后功能性移植β细胞储备是否正常尚不清楚，胰岛素分泌的传统测量方法能否准确反映功能性β细胞量也不清楚。为了确定胰岛移植后的胰岛素分泌储备，我们对8例肝内胰岛自体移植受者进行了精氨酸诱导胰岛素分泌的葡萄糖增强作用（GPAIS）研究。所有8名受试者（以及匹配的健康对照）在移植后49±12个月进行了横断面研究，4名受试者在移植前后进行了研究。受试者平均接受了479,000±79,000个胰岛，研究时均为胰岛素非依赖且血糖正常。两个研究组中，胰岛移植后对精氨酸、葡萄糖和GPAIS的急性胰岛素反应均显著降低。重要的是，这三种反应的幅度与移植胰岛的数量高度相关（对葡萄糖的反应：r = 0.84，P < 0.01；对精氨酸的反应：r = 0.69，P < 0.05；对GPAIS的反应 = 0.81，P < 0.01）。半胰切除和正常对照受试者的数据总体上与回归线一致。这些发现表明，尽管血糖正常且胰岛素非依赖，但肝内胰岛移植受者的功能性β分泌储备显著降低，且胰岛移植后，可通过测量葡萄糖和精氨酸诱导的胰岛素反应来估计功能性β细胞量。因此，这些测量可用于估计人类肝内移植后存活胰岛的数量和功能能力。
