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

Authors
 Sang-Guk Lee  ;  Ye Seal Yim  ;  Yong-Ho Lee  ;  Byung-Wan Lee  ;  Hyon-Suk Kim  ;  Kyung-Sup Kim  ;  Yong-Wha Lee  ;  Jeong-Ho Kim 
Citation
 Diabetes Research and Clinical Practice, Vol.140 : 107-117, 2018 
Journal Title
 Diabetes Research and Clinical Practice 
ISSN
 0168-8227 
Issue Date
2018
Keywords
Amino acids profile ; Inflammatory cytokines ; Insulin resistance ; Proteolysis ; Type 2 diabetes mellitus
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-alpha, and IL-6 were analyzed in fasting serum samples from a total of 198 individuals (56 drug-naive 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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0168822718301001
DOI
10.1016/j.diabres.2018.03.028
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jeong Ho(김정호) ORCID logo https://orcid.org/0000-0003-2479-0548
Kim, Hyon Suk(김현숙) ORCID logo https://orcid.org/0000-0001-5662-7740
Lee, Byung Wan(이병완) ORCID logo https://orcid.org/0000-0002-9899-4992
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162596
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