2015
DOI: 10.1016/j.metabol.2015.01.008
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Effect of Insulin Sensitizer Therapy on Amino Acids and Their Metabolites

Abstract: Aims 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. Methods We performed a secondary analysis of a randomized, double-blind, placebo… Show more

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Cited by 84 publications
(81 citation statements)
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“…Of note, metformin also reduced serum concentrations of arginine in their unadjusted model. These results corroborate our prior findings that 3 months of metformin plus pioglitazone therapy reduced plasma concentrations of citrulline and arginine in overweight/obese adults with impaired fasting glucose (9). Likewise, acutely administering metformin reduced plasma citrulline concentrations in African Americans without diabetes (10).…”
supporting
confidence: 90%
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“…Of note, metformin also reduced serum concentrations of arginine in their unadjusted model. These results corroborate our prior findings that 3 months of metformin plus pioglitazone therapy reduced plasma concentrations of citrulline and arginine in overweight/obese adults with impaired fasting glucose (9). Likewise, acutely administering metformin reduced plasma citrulline concentrations in African Americans without diabetes (10).…”
supporting
confidence: 90%
“…Indeed, in the "human discovery" study, serum concentrations of citrulline, arginine, ornithine, and urea were all lower (based on the unadjusted model) in the metformin-treated versus untreated participants with T2D (8). Metformininduced reductions in these metabolites likely reflect reductions in urea biosynthesis, secondary to reductions in gluconeogenesis (9). Reductions in serum/plasma amino acids may also result in reduced pressure for the liver and kidneys to perform high rates of urea detoxification secondary to reductions in protein breakdown.…”
mentioning
confidence: 98%
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“…In a subset of patients ( n = 30) with overnight fasted, pre-operative, serum that were stored at −80 °C, we measured serum concentrations of branched-chain amino acids (leucine, isoleucine, and valine) and aromatic amino acids (phenylalanine and tyrosine) by liquid chromatography (LC) mass spectrometry as previously described [13] and concentrations of short-chain fatty acids (isobutyric acid, butyric acid, isovaleric acid, valeric acid, isocaproic acid, and hexanoic acid) by gas chromatography (GC) mass spectrometry as previously described [14]. All measures for isobutyric acid were above the standard curve; due to sample constraints, we were unable to re-run a diluted sample to obtain these values, and therefore we excluded these data from the present analysis.…”
Section: Methodsmentioning
confidence: 99%