Homoarginine supplementation improves blood glucose in diet-induced obese mice
Homoarginine supplementation improves blood glucose in diet-induced obese mice
复制标题
DOI：
10.1007/s00726-015-2022-1
复制
发表时间：
2015-09-01
期刊：
影响因子：
3.5
通讯作者：
Choe, Chi-un
中科院分区：
文献类型：
--
作者：
Stockebrand, Malte;Hornig, Soenke;Choe, Chi-un
l-高精氨酸（hArg）是一种内源性氨基酸，已成为中风和心血管疾病的新生物标志物。低循环hArg水平与死亡率和血管事件增加相关，而最近的数据显示循环hArg与代谢性血管风险因素如肥胖或血糖水平之间呈正相关。然而，目前尚不清楚hArg水平是否与代谢参数有因果关系。因此，我们的研究目的是调查是否hArg直接影响体重，血糖，葡萄糖耐量或胰岛素敏感性。在这里，我们表明，hArg补充（14和28毫克/毫升口服每饮用水）改善高脂饮食（HFD）的小鼠的血糖水平，分别减少7.3 +/- A 3.7或13.4 +/- A 3.8%。空腹胰岛素浓度受到轻微但显著的影响（分别为对照动物的63.8 +/- A 11.3或162.1 +/- A 39.5%），而体重和葡萄糖耐量不变。补充动物中hArg血浆浓度大幅增加（对照动物的327.5 +/- A 40.4或627.5 +/- A 60.3%，在动物变得肥胖后，（HFD后对照动物中分别为129.9 +/- A 16.6%与140.1 +/- A 8.5或206.3 +/- A 13.6%）。这种hArg降低效应可能导致血浆hArg水平与中风和心血管结局的负相关性与另一方面与肥胖和血糖等心血管危险因素的直接相关性之间的差异，这已在人体研究中观察到。我们的研究结果表明，hArg的降糖作用可能反映了一种补偿机制，在肥胖个体中通过hArg上调降低血糖，而不直接影响体重或糖耐量。
l-Homoarginine (hArg) is an endogenous amino acid which has emerged as a novel biomarker for stroke and cardiovascular disease. Low circulating hArg levels are associated with increased mortality and vascular events, whereas recent data have revealed positive correlations between circulating hArg and metabolic vascular risk factors like obesity or blood glucose levels. However, it is unclear whether hArg levels are causally linked to metabolic parameters. Therefore, the aim of our study was to investigate whether hArg directly influences body weight, blood glucose, glucose tolerance or insulin sensitivity. Here, we show that hArg supplementation (14 and 28 mg/mL orally per drinking water) ameliorates blood glucose levels in mice on high-fat diet (HFD) by a reduction of 7.3 +/- A 3.7 or 13.4 +/- A 3.8 %, respectively. Fasting insulin concentrations were slightly, yet significantly affected (63.8 +/- A 11.3 or 162.1 +/- A 39.5 % of control animals, respectively), whereas body weight and glucose tolerance were unaltered. The substantial augmentation of hArg plasma concentrations in supplemented animals (327.5 +/- A 40.4 or 627.5 +/- A 60.3 % of control animals, respectively) diminished profoundly after the animals became obese (129.9 +/- A 16.6 % in control animals after HFD vs. 140.1 +/- A 8.5 or 206.3 +/- A 13.6 %, respectively). This hArg-lowering effect may contribute to the discrepancy between the inverse correlation of plasma hArg levels with stroke and cardiovascular outcome, on the one hand, and the direct correlation with cardiovascular risk factors like obesity and blood glucose, on the other hand, that has been observed in human studies. Our results suggest that the glucose-lowering effects of hArg may reflect a compensatory mechanism of blood glucose reduction by hArg upregulation in obese individuals, without directly influencing body weight or glucose tolerance.