Gly-Ala-Gly-Val-Gly-Tyr, a novel synthetic peptide, improves glucose transport and exerts beneficial lipid metabolic effects in 3T3-L1 adipoctyes

초록

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-gamma (PPAR gamma) and fatty acid synthase (FAS) in mature 3T3-L1 adipocytes which was coiroborated with decreased lipid accumulation by GAGVGY treatment Additionally in cells undergoing differentiation mRNA levels of adipogenic genes including PPAR gamma and CCAAT/enhancer binding protein alpha (C/EBP alpha) 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 ID (C) 2010 Elsevier BV All rights reserved

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