Metabolic effects of restoring partial β-cell function after islet allotransplantation in type 1 diabetic patients
Metabolic effects of restoring partial β-cell function after islet allotransplantation in type 1 diabetic patients
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DOI：
10.2337/diabetes.50.2.277
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发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Bretzel, RG
中科院分区：
文献类型：
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作者：
Luzi, L;Perseghin, G;Bretzel, RG
成功的门脉内胰岛移植使糖尿病患者的糖代谢正常化。迄今为止，人类胰岛移植后通常不能实现完全功能，大多数移植物的特征是仅具有部分功能。此外，完全功能的持续时间是可变的，并且不能用现有方法充分预测。相比之下，大多数移植物在很长一段时间内保持部分功能。我们假设部分功能可以恢复正常的蛋白质和脂质代谢在糖尿病患者。我们研究了45例胰岛移植后的糖尿病患者。输注标记葡萄糖和亮氨酸以评估1）6例门静脉内胰岛移植后功能完全的1型糖尿病患者的全身葡萄糖和蛋白质周转（FF组; C肽> 0.6 nmol/l;每日胰岛素剂量0.03 +/- 0.02 U; kg 1体重return（1）;空腹血糖<7.7mmol/l，HbA 1c <6.5%; 2）部分功能（PF组）17例，C肽> 0.16nmol/l，胰岛素用量<0.4U。kg（-1）体重无功能组（NF组，C肽<0.16nmol/l，胰岛素用量> 0.4U）9例。kg（-1）体重（-1）天）;（4）6例慢性葡萄膜炎患者作为对照组（CU组）。通过预充-连续输注[3，3，3-H-2（3）]亮氨酸，在另外5名PF和5名健康志愿者中评估肝脏白蛋白合成。FF组的胰岛素需求比移植前水平低97%，PF组比移植前水平低57%。在基础状态下，PF组的血糖浓度略高于FF组（P = 0.249）和CU组（P = 0.08），但与NF组相比有所改善（P < 0.01）。PF、FF和CU组的血浆亮氨酸（101.1 +/- 5.9 mol/l）和支链氨基酸（337.6 +/- 16.6 μ mol/l）相似，显著低于NF组（P < 0.01）。胰岛素输注期间，NF组葡萄糖代谢清除率低于其他组（P < 0.01）。PF、FF和CU组的基础和胰岛素刺激的蛋白水解和蛋白合成率相当，但NF组显著更高（P = 0.05）。此外，PF组的肝脏白蛋白合成正常。PF和FF组的血浆游离脂肪酸浓度与CU组相似，但NF组在钳夹期间显示出降低的胰岛素依赖性抑制。我们的结论是，恢复类似60%的内源性胰岛素分泌是能够正常化的蛋白质和脂质代谢的改变，在1型糖尿病肾受体，尽管慢性免疫抑制治疗。本研究的结果表明，胰岛移植的“成功”可能是最好的定义由一些代谢标准，而不仅仅是葡萄糖浓度/代谢。
Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U . kg 1 body wt . day(-1); fasting plasma glucose < 7.7 mmol/l; HbA(1c) 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U . kg(-1) body wt . day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U . kg(-1) body wt . day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-H-2(3)]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levers for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 mol/l) and branched-chain amino acids (337.6 +/- 16.6 mu mol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of similar to 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.