title: In vivo and in vitro application of black soybean peptides in the amelioration of endoplasmic reticulum stress and improvement of insulin resistance.
abstract: OBJECTIVE
  Hepatic endoplasmic reticulum (ER) stress plays a key role in the development of obesity-induced insulin resistance. This study evaluated the effects of peptides from black soybean (BSP) on ER stress and insulin signaling in vitro and in vivo.
  
  
  METHODS
  Using C2C12 myotubes or HepG2 cells, we evaluated the effects of BSP on the expression of proteins involved in insulin signaling and in the ER stress response in insulin-sensitive or insulin-resistant cells. BSP was given orally to db/db mice for 5weeks to investigate its antidiabetic effects in vivo and the underlying mechanisms.
  
  
  RESULTS
  BSP increased GLUT4 translocation and glucose transport in myotubes and stimulated Akt-mediated glycogen synthase kinase-3beta (GSK-3beta) and Foxo1 phosphorylation in HepG2 cells. BSP significantly restored the suppression of insulin-mediated Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the activation of ER stress-responsive proteins by thapsigargin. BSP also significantly reduced blood glucose and improved glucose tolerance in db/db mice. The serum lipid profile (triglyceride and high-density lipoprotein concentrations) improved concomitantly with the BSP-induced downregulation of hepatic fatty acid synthase expression in db/db mice. Consistent with the results observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress response in diabetic mice concomitantly with an increased expression of phospho-Foxo1.
  
  
  CONCLUSIONS
  A peptide mixture, BSP, showed beneficial effects through multiple mechanisms involving the suppression of hepatic ER stress and restoration of insulin resistance, suggesting that it has potential as an antidiabetic agent.
authors.affiliation: Department of Pharmacology and Medicinal Toxicology Research Center, Inha Research Institute for Medical Sciences, College of Medicine, South Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Jang
authors.forename: Jeong Hyeon
authors.initials: JH
authors.lastname: Ko
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Ahn
authors.forename: Ho-Hyun
authors.initials: HH
authors.lastname: Lee
authors.forename: Jae-Kil
authors.initials: JK
authors.lastname: Shin
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Chang
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Park
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*; D013312:Stress, Physiological / Q000187:drug effects*; D019284:Thapsigargin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D008075:Lipoproteins, HDL; D010455:Peptides; D010940:Plant Proteins; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D014280:Triglycerides; D019284:Thapsigargin; D064429:Fatty Acid Synthases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3