In vivo and in vitro application of black soybean peptides in the amelioration of endoplasmic reticulum stress and improvement of insulin resistance.
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.
Jang
Eun-Hee
EH
Department of Pharmacology and Medicinal Toxicology Research Center, Inha Research Institute for Medical Sciences, College of Medicine, South Korea.
Ko
Jeong Hyeon
JH
Ahn
Chang-Won
CW
Lee
Ho-Hyun
HH
Shin
Jae-Kil
JK
Chang
Seong-Jun
SJ
Park
Chang-Shin
CS
Kang
Ju-Hee
JH
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
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