CYC31, A Natural Bromophenol PTP1B Inhibitor, Activates Insulin Signaling and Improves Long Chain-Fatty Acid Oxidation in C2C12 Myotubes

Mar Drugs. 2020 May 19;18(5):267. doi: 10.3390/md18050267.

Abstract

3-bromo-4,5-Bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (CYC31) is a bromophenol protein tyrosine phosphatase 1B (PTP1B) inhibitor isolated from the red alga Rhodomela confervoides. Here, the effect of CYC31 on the insulin signaling and fatty-acid-induced disorders in C2C12 myotubes was investigated. Molecular docking assay showed that CYC31 was embedded into the catalytic pocket of PTP1B. A cellular study found that CYC31 increased the activity of insulin signaling and promoted 2-NBDG uptake through GLUT4 translocation in C2C12 myotubes. Further studies showed that CYC31 ameliorated palmitate-induced insulin resistance in C2C12 myotubes. Moreover, CYC31 treatment significantly increased the mRNA expression of carnitine palmitoyltransferase 1B (CPT-1B) and fatty acid binding protein 3 (FABP3), which was tightly linked with fatty acid oxidation. These findings suggested that CYC31 could prevent palmitate-induce insulin resistance and could improve fatty acid oxidation through PTP1B inhibition.

Keywords: C2C12; CYC31; PTP1B inhibitor; fatty acid oxidization; insulin resistance.

MeSH terms

  • Benzhydryl Compounds / pharmacology*
  • Catechols / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Insulin / metabolism
  • Muscle Fibers, Skeletal / metabolism
  • Oxidation-Reduction
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Rhodophyta*

Substances

  • 3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol
  • Benzhydryl Compounds
  • Catechols
  • Enzyme Inhibitors
  • Insulin
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1