Effect of insulin sensitizer therapy on amino acids and their metabolites.
Effect of insulin sensitizer therapy on amino acids and their metabolites.
复制标题
胰岛素敏化剂治疗对氨基酸及其代谢产物的影响。
DOI：
10.1016/j.metabol.2015.01.008
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Nair KS
中科院分区：
文献类型：
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作者：
Irving BA;Carter RE;Soop M;Weymiller A;Syed H;Karakelides H;Bhagra S;Short KR;Tatpati L;Barazzoni R;Nair KS
先前的研究已经报道，血浆中几种血浆氨基酸（AA），特别是支链（BCAA）和芳香族AA的浓度升高可预测2型糖尿病的发病。我们试图检验以下假设：在空腹血糖受损或未经治疗的糖尿病超重/肥胖成年人中，循环中的支链氨基酸、芳香族AA和相关AA代谢物对胰岛素增敏剂的使用反应下降。我们对一项随机、双盲、安慰剂对照研究进行了二次分析，该研究在25名空腹血糖受损或未经治疗的糖尿病超重/肥胖（BMI~30 kg/m2）成年人中进行。参与者被随机分配到三个月的吡格列酮（每天45 mg）+二甲双胍（1000 mg，每天两次，N = 12名参与者）或安慰剂（N = 13）。我们测量了胰岛素敏感性的正常血糖-高胰岛素钳夹和空腹浓度的AA和AA代谢物，使用超高压液相色谱串联质谱法之前和之后的三个月的干预。与安慰剂治疗相比，显著增强胰岛素敏感性的胰岛素增敏剂治疗减少了33种AA和AA代谢物中的9种。此外，胰岛素增敏剂治疗显著减少了三种功能性聚集的AA和代谢物对：i）苯丙氨酸/酪氨酸，ii）瓜氨酸/精氨酸，和iii）赖氨酸/α-氨基己二酸。胰岛素增敏剂治疗3个月后，几种AA和AA代谢物的血浆浓度降低，这支持了胰岛素敏感性降低会改变AA和AA代谢物的概念。
Prior studies have reported that elevated concentrations of several plasma amino acids (AA) in plasma, particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI~30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.