Gly-Ala-Gly-Val-Gly-Tyr, a novel synthetic peptide, improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipoctyes.
Recently, it has been demonstrated that fibroin and fibroin-derived peptides enhances insulin sensitivity and glucose metabolism in adipocytes. Here, we show that a synthetic hexapeptide Gly-Ala-Gly-Val-Gly-Tyr (GAGVGY) derived from repetitive amino acid sequence of fibroin improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipocytes. GAGVGY increases both basal and insulin-stimulated glucose uptake through enhancement of GLUT1 expression and PI 3-K-dependent GLUT4 translocation, respectively. GAGVGY treatment also led to a significant reduction in the expression of lipogenic genes including sterol regulatory element binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-γ (PPARγ), and fatty acid synthase (FAS) in mature 3T3-L1 adipocytes, which was corroborated with decreased lipid accumulation by GAGVGY treatment. Additionally, in cells undergoing differentiation, mRNA levels of adipogenic genes including PPARγ and CCAAT/enhancer binding protein α (C/EBPα), stearoyl-CoA desaturase 1 (SCD1), and FAS were suppressed by GAGVGY. Furthermore, GAGVGY increased AMP-activated protein kinase (AMPK) phosphorylation and adiponectin secretion in 3T3-L1 adipocytes. The latter effect was supported with evidence showing increased AMPK activation in C2C12 myocytes treated with 3T3-L1-adipocyte-conditioned medium. Together, our data suggest that GAGVGY has multiple beneficial effects on glucose and lipid metabolism, and would control hyperglycemia without the adverse effect of weight gain.
School of Life Science, Handong Global University, Pohang, Kyungbuk 791-708, Republic of Korea.
Eun-Do
ED
Kim
Eunha
E
Kim
Jung-Han
JH
Lee
Chang-Kee
CK
Hyun
D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D052242:Adiponectin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D000263:Adenylate Kinase; D005947:Glucose