BET bromodomain inhibition suppresses TH17-mediated pathology

Cytokines;Chemokines;细胞因子;趋化因子;MSD;Cytokines;Chemokines
浏览次数:13 分享:

Mele DA, Salmeron A, Ghosh S, Huang HR, Bryant BM, Lora JM.

  • J Exp Med.
  • 2013
  • 17.579
  • 123(10):4309-17.
  • Human,Mouse,Non-Human Primate,Rat
  • MSD
  • Plasma
  • 免疫/内分泌
  • T细胞
  • IL-10, IL-17A

相关货号

LXMH07-1LXMH07-4LXMH09-1LXMH09-2LXMH09-3LXMH09-4LXMH10-3LXMH10-4LXMH10-5LXMH10-9LXMH111-1LXMH14-1LXMH37-1LXMH40-1LXMH44-1LXMH46-1LXMH54-1LXMH71-1LXMH87-1LXMM08-1LXMM09-2LXMM10-2LXMM10-4LXMM14-1LXMM50-1LXMM58-1LXMN05-1LXMN06-3LXMN09-1LXMN09-2LXMN09-3LXMN09-4LXMN10-3LXMN12-1LXMN24-2LXMN61-1LXMR09-1

Abstract

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.
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