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Effect of insulin sensitizer therapy on amino acids and their metabolites.


ABSTRACT: 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/?-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.

SUBMITTER: Irving BA 

PROVIDER: S-EPMC4525767 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Effect of insulin sensitizer therapy on amino acids and their metabolites.

Irving Brian A BA   Carter Rickey E RE   Soop Mattias M   Weymiller Audrey A   Syed Husnain H   Karakelides Helen H   Bhagra Sumit S   Short Kevin R KR   Tatpati Laura L   Barazzoni Rocco R   Nair K Sreekumaran KS  

Metabolism: clinical and experimental 20150122 6


<h4>Aims</h4>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.<h4>Methods</h4>We performed a secondary analysis of a randomized, dou  ...[more]

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