Fibroin-Derived Peptides Stimulate Glucose Transport in Normal and Insulin-Resistant 3T3-L1 Adipocytes

Abstract

Fibroin, the protein of silk, and hydrolyzed fibroin have recently been described to enhance insulin sensitivity and glucose metabolism in 3T3-L1 adipocytes. Here, we report that a series of synthetic peptides derived from the fibroin sequence have enhancing effects on glucose transport in normal and insulin-resistant 3T3-L1 cells. We observed that, among several enzymatic hydrolysates of fibroin, the chymotryptic and peptic hydrolysates were significantly more effective than others in augmenting insulin-stimulated glucose uptake in both cells. We synthesized several peptides of repetitive sequences in fibroin. Treatment with synthesized hexapeptides enhanced insulin-stimulated glucose uptake more than tri-, tetra-or pentapeptides. Among those, the effect of Gly-Ala-Gly-Ala-Gly-Tyr (GAGAGY) was most robust, and especially its activity of blocking off the chronic-insulin-induced loss of insulin-stimulated uptake was remarkable. Data reveal that the residues of tyrosine situated at the ends of the peptides play a critical role for exerting their activities. We demonstrate that the insulin-sensitizing effect of GAGAGY is due to enhancement of phosphoinositide 3-kinase (PI 3-K) signaling pathway. The GAGAGY-induced insulin-stimulated glucose uptake was sensitive to inhibition of PI 3-K by wortmannin. Phosphorylation of Akt was also elevated in GAGAGY-treated cells. Furthermore, GAGAGY significantly increased insulin-induced glucose transporter 4 (GLUT4) translocation without affecting the synthesis of GLUT4. Our findings suggest that fibroin-derived peptides such as GAGAGY could be considered as novel insulin-sensitizing agents with an activity of blocking the development of insulin resistance.

Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

“…14 Besides, fibroin is not only an inert drug carrier. The peptides resulting from its hydrolysis have shown therapeutic potential, for instance, in the stimulation of glucose transport in normal and insulin-resistant 3T3-L1 adipocytes 15 or in the proliferation of fibroblasts in wound healing models. 11 Kim et al also reported the anti-inflammatory activity of fibroin peptides in a mice edema model of inflammation.…”

Biocomposite nanofibrous strategies for the controlled release of biomolecules for skin tissue regeneration

“…The reason may be the capability of SF to motivate several cell signaling pathways leading to improved secretion of collagen matrix compared to PLACL scaffolds. 43 Generally, PLACL biopolymers support the cell growth by adding VE; Cur induce the secretion of ECM in fibroblast cells. The results …”

Effect of Silk Fibroin Hydrolysate on the Apoptosis of MCF-7 human Breast Cancer Cells

“…Hydrolysates of silk fibroin (HSF) are water-soluble peptides that have been investigated as food and dietary supplements. HSF contains 18 different amino acids, including Gly (45.9%), Ala (30.3%), Ser (12.1%), Tyr (5.3%), and Val (1.8%) (Kim et al, 2009;Tsukada et al, 1994). Numerous studies have documented a range of effects of HSF, including moisturizing effects (Nishida et al, 2010), wrinkle reduction, inhibition of tyrosinase (Kato et al, 1998), and apoptosis (Acharya et al, 2008).…”