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Pourquoi le diabète augmente le niveau de BCAA sanguins?

10/06/2018 | Etudes Compléments alimentaires et Etudes Perte de poids et Etudes Anti-âge

 

Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines
Diabetes Research and Clinical Practice Volume 140, June 2018, Pages 107-117               Sang-GukLee
Highlights
• Serum branched chain amino acids (BCAAs) were increased in type 2 diabetes mellitus.
• Serum non-BCAAs were also elevated in patients with type 2 diabetes.
• HOMA-IR and pro-inflammatory cytokines were independent predictors of amino acid.
• Insulin resistance or inflammatory cytokines could induce skeletal muscle proteolysis.
• Elevated serum amino acids are an early manifestation of impaired insulin action.

Aims
We evaluated specific alterations in amino acids (AAs) profile in patients with type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) compared with healthy controls. In addition, we tried to find the mechanisms behind these AA alterations.

Methods
Twenty AAs, TNF-α, and IL-6 were analyzed in fasting serum samples from a total of 198 individuals (56 drug-naïve patients with T2DM, 69 patients IFG, and 73 healthy controls). The C2C12 mouse myoblast cell lines were used to examine the changes of MAFbx and MuRF1 expressions, which are muscle specific E3 ligases acting as major mediators of skeletal muscle proteolysis, after development of insulin resistance induced by palmitate treatment.

Results
In addition to branched chain amino acids BCAAs, fasting serum AAs such as glutamic acid, lysine, phenylalanine, arginine, alanine, tyrosine, aspartic acid, were higher in patients with T2DM and intermediately elevated in patients with IFG compared with normoglycemic controls. These serum AA concentrations positively correlated with fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. In addition, HOMA-IR and pro-inflammatory cytokines were two important independent predictors of serum AA levels. In vitro experiments showed that palmitate treatment in C2C12 myotubes induced insulin resistance, increased pro-inflammatory cytokine gene expression, and increased MAFbx gene and protein expression.

Conclusions
The increase in fasting serum AAs can be an early manifestation of insulin resistance. Increased muscle proteolysis induced by insulin resistance and inflammatory cytokines can be a possible mechanism for the rise in serum AA levels.

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