Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines

Sang Guk Lee, Ye Seal Yim, Yong ho Lee, byungwan lee, Hyonsuk Kim, Kyung Sup Kim, Yong Wha Lee, Jeong Ho Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)107-117
Number of pages11
JournalDiabetes Research and Clinical Practice
Volume140
DOIs
Publication statusPublished - 2018 Jun 1

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Insulin Resistance
Fasting
Cytokines
Amino Acids
Serum
Type 2 Diabetes Mellitus
Glucose
Palmitates
Proteolysis
Homeostasis
Gene Expression
Muscles
Branched Chain Amino Acids
Ubiquitin-Protein Ligases
Myoblasts
Skeletal Muscle Fibers
Phenylalanine
Aspartic Acid
Alanine
Lysine

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Lee, Sang Guk ; Yim, Ye Seal ; Lee, Yong ho ; lee, byungwan ; Kim, Hyonsuk ; Kim, Kyung Sup ; Lee, Yong Wha ; Kim, Jeong Ho. / Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines. In: Diabetes Research and Clinical Practice. 2018 ; Vol. 140. pp. 107-117.
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Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines. / Lee, Sang Guk; Yim, Ye Seal; Lee, Yong ho; lee, byungwan; Kim, Hyonsuk; Kim, Kyung Sup; Lee, Yong Wha; Kim, Jeong Ho.

In: Diabetes Research and Clinical Practice, Vol. 140, 01.06.2018, p. 107-117.

Research output: Contribution to journalArticle

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T1 - Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines

AU - Lee, Sang Guk

AU - Yim, Ye Seal

AU - Lee, Yong ho

AU - lee, byungwan

AU - Kim, Hyonsuk

AU - Kim, Kyung Sup

AU - Lee, Yong Wha

AU - Kim, Jeong Ho

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N2 - 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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