Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients
Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients
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DOI：
10.2337/diacare.24.5.875
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发表时间：
2001-05-01
期刊：
影响因子：
16.2
通讯作者：
Alberti, KGMM
中科院分区：
文献类型：
--
作者：
Piatti, P;Monti, LD;Alberti, KGMM
目的：本研究的目的是评估长期给予l -精氨酸是否能够通过NO/环鸟苷-3',5'-环单磷酸（cGMP）途径的正常化来改善12例瘦型2型糖尿病患者的外周和肝脏胰岛素敏感性。研究设计与方法：双盲研究为期3个月。在第一个月，患者接受常规饮食治疗。然后他们被随机分成两组。在第1组中，患者采用饮食加安慰剂（每天口服3次）治疗2个月，第2组患者采用饮食加安慰剂（每天口服3次）治疗1个月，然后采用饮食加l -精氨酸（每天3次，3g）治疗1个月。在治疗的第一个月和第二个月结束时，患者接受正血糖-高胰岛素钳夹联合[6.6-H-2(2)]葡萄糖输注。10名正常受试者接受与对照组相同的测试。结果：在第1组，在整个过程中没有观察到基础cGMP水平、收缩压、前臂血流葡萄糖处置和内源性葡萄糖生成的变化。在第2组中，l -精氨酸使基础cGMP水平正常化，使前臂血流量增加36%，夹钳期间葡萄糖处理增加34%，而收缩压和内源性葡萄糖产生分别降低14%和29%。然而，与正常受试者相比，l -精氨酸处理不能完全克服葡萄糖处理的缺陷。结论：l -精氨酸治疗可显著改善2型糖尿病患者的外周和肝脏胰岛素敏感性，但不能完全恢复正常。
OBJECTIVE- The aim of this study was to evaluate whether long-term administration of L-arginine acting through a normalization of NO/cyclic-guanosine-3',5'-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients.RESEARCH DESIGN AND METHODS- A double-blind study was performed for 3 months. In the first month, patients were treated with their usual diet. Then they were randomly allocated into two groups. In group 1, patients were treated with diet plus placebo (orally three times per day) for 2 months, in group 2 patients were treated for 1 month with diet plus placebo (orally, three times per day) and then for 1 month with diet plus L-arginine (3 g three times per day). At the end of the first and the second month of therapy, patients underwent a euglycemic-hyperinsulinemic clamp combined with [6.6-H-2(2)]glucose infusion. A total of 10 normal subjects underwent the same test as control subjects.RESULTS- In group 1, no changes in basal cGMP levels, systolic blood pressure, forearm blood flow glucose disposal, and endogenous glucose production were observed throughout. In group 2, L-arginine normalized basal cGMP levels and significantly increased forearm blood flow by 36% and glucose disposal during the clamp by 34%, whereas it decreased systolic blood pressure and endogenous glucose production by 14 and 29%, respectively. However, compared with normal subjects, L-arginine treatment was not able to completely overcome the defect in glucose disposal.CONCLUSIONS- L-Arginine treatment significantly improves but does not completely normalize peripheral and hepatic insulin sensitivity in type 2 diabetic patients.