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Publication
Plasma amino acid and metabolite signatures tracking diabetes progression in the
UCD-T2DM rat model.
Authors Piccolo BD, Graham JL, Stanhope KL, Fiehn O, Havel PJ, Adams SH
Submitted By Submitted Externally on 3/23/2018
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2016
Date Published 6/1/2016
Volume : Pages 310 : E958 - 69
PubMed Reference 27094034
Abstract Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are
observed in human insulin resistance and type 2 diabetes mellitus (T2DM);
however, there has been some controversy with respect to the passive or
causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma
BCAA and other metabolites were assessed in lean control Sprague-Dawley rats
(LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e.,
prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of
diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated
only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This
was in contrast to decreased plasma concentrations of several other amino acids
in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and
Trp). BCAAs were positively correlated with fasting glucose and negatively
correlated with plasma insulin, total body weight, total adipose tissue weight,
and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis
revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids,
amino acid derivatives, 1,5-anhydroglucitol, and conduritol-ß-opoxide and higher
concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid,
lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The
UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo
post-onset of diabetes. With the acknowledgement that this is a rodent model of
T2DM, the results indicate that elevated plasma BCAA concentrations are not
necessary or sufficient to elicit an insulin resistance or T2DM onset.




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