Abstract
Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA), Ile-Ala-Val-Pro-Thr-Gly-Val-Ala (IAVPTGVA) and Leu-Pro-Tyr-Pro (LPYP), three peptides deriving from soy glycinin hydrolysis, are known to regulate cholesterol metabolism in human hepatic HepG2 cells. We have recently demonstrated that the mechanism of action involves the activation of adenosine monophosphate-activated protein kinase (AMPK). This fact suggested a potential activity of the same peptides on glucose metabolism that prompted us to also investigate this aspect in the same cells. After treatment with IAVPGEVA, IAVPTGVA and LPYP, HepG2 cells were analyzed using a combination of molecular techniques, including western blot analysis, glucose uptake experiments and fluorescence microscopy evaluation. The results showed that these peptides are indeed able to enhance the capacity of HepG2 cells to uptake glucose, via glucose transporter 1 GLUT1 and glucose transporter 4 GLUT4 activation, through the stimulation of protein kinase B Akt and adenosine monophosphate-activated protein kinase AMPK pathways, both involved in glucose metabolism.
Highlights
Soy foods provide useful health benefits [1,2,3], especially in the area of hypercholesterolemia prevention [4,5]
In the framework of a research aimed at assessing the role of proteins and peptides in this activity [6,7,8], we have recently characterized the molecular mechanism through which three peptides deriving from soy glycinin digestion with trypsin or pepsin, namely: Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA), Ile-Ala-Val-Pro-Thr-Gly-Val-Ala (IAVPTGVA) and Leu-Pro-Tyr-Pro (LPYP) [9], modulate cholesterol metabolism in HepG2 cells [10]
Our experiments have demonstrated that these peptides are able to increase the low density lipoprotein (LDL) receptor (LDLR) protein level, with the consequence of an enhanced capacity of HepG2 cells to uptake LDL [10]
Summary
Soy foods provide useful health benefits [1,2,3], especially in the area of hypercholesterolemia prevention [4,5]. In the framework of a research aimed at assessing the role of proteins and peptides in this activity [6,7,8], we have recently characterized the molecular mechanism through which three peptides deriving from soy glycinin digestion with trypsin or pepsin, namely: Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA), Ile-Ala-Val-Pro-Thr-Gly-Val-Ala (IAVPTGVA) and Leu-Pro-Tyr-Pro (LPYP) [9], modulate cholesterol metabolism in HepG2 cells [10] These peptides were selected because preceding investigations by other Authors had shown that they inhibit in vitro the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) [9,11,12]. Taking into account all these evidences, the objectives of the present investigation were twofold: (a) to verify whether IAVPGEVA, IAVPTGVA and LPYP are able to modulate glucose metabolism in HepG2 cells; (b) to accomplish a molecular characterization of the stimulated pathways
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