Irving Brian A, Carter Rickey E, Soop Mattias, Weymiller Audrey, Syed Husnain, Karakelides Helen, Bhagra Sumit, Short Kevin R, Tatpati Laura, Barazzoni Rocco, Nair K Sreekumaran
Division of Endocrinology, Endocrinology Research Unit, Mayo Clinic College of Medicine, Rochester, MN.
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
Metabolism. 2015 Jun;64(6):720-8. doi: 10.1016/j.metabol.2015.01.008. Epub 2015 Jan 22.
Prior studies have reported that elevated concentrations of several plasma amino acids (AA), 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 ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg 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.
先前的研究报道，几种血浆氨基酸（AA）浓度升高，特别是支链氨基酸（BCAA）和芳香族氨基酸可预测2型糖尿病的发病。我们试图验证这样一个假设：在空腹血糖受损或未经治疗的超重/肥胖成年人中，使用胰岛素增敏剂后，循环中的支链氨基酸、芳香族氨基酸及相关氨基酸代谢产物会减少。
我们对一项随机、双盲、安慰剂对照研究进行了二次分析，该研究纳入了25名超重/肥胖（BMI约30kg/m²）且空腹血糖受损或未经治疗的糖尿病成年人。参与者被随机分为两组，一组接受为期三个月的吡格列酮（每日45mg）加二甲双胍（每日两次，每次1000mg，共12名参与者）治疗，另一组接受安慰剂治疗（13名参与者）。在为期三个月的干预前后，我们通过正常血糖高胰岛素钳夹技术测量胰岛素敏感性，并使用超高效液相色谱串联质谱法测量氨基酸和氨基酸代谢产物的空腹浓度。
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使所测量的33种氨基酸和氨基酸代谢产物中的9种减少。此外，胰岛素增敏剂治疗显著降低了三个功能聚类的氨基酸和代谢产物对：i）苯丙氨酸/酪氨酸，ii）瓜氨酸/精氨酸，以及iii）赖氨酸/α-氨基己二酸。
三个月的胰岛素增敏剂治疗后，几种氨基酸和氨基酸代谢产物的血浆浓度降低，这支持了胰岛素敏感性降低会改变氨基酸和氨基酸代谢产物的观点。
