PMID- 32857071 OWN - NLM STAT- MEDLINE DCOM- 20210722 LR - 20210722 IS - 2042-650X (Electronic) IS - 2042-6496 (Linking) VI - 11 IP - 9 DP - 2020 Sep 23 TI - Peptides from walnut (Juglans mandshurica Maxim.) protect hepatic HepG2 cells from high glucose-induced insulin resistance and oxidative stress. PG - 8112-8121 LID - 10.1039/d0fo01753a [doi] AB - Oxidative stress is an important factor in the pathogenesis of insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Bioactive peptides from nuts have been shown to alleviate oxidative stress and IR. However, the specific mechanisms underlying their activity remain unclear. This study investigated the protective effects of three novel peptides derived from Juglans mandshurica Maxim., LVRL, LRYL, and VLLALVLLR, against high glucose-induced IR and oxidative stress in HepG2 cells. The possible mechanisms underlying these effects were also elucidated. The walnut-derived peptides improved glucose consumption, glucose uptake, and glucose transporter type 4 (GLUT4) translocation, and elevated the phosphorylation of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt). They also increased the activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD), the nuclear transport of nuclear factor E2-related factor 2 (Nrf2), and the protein expression of heme oxygenase-1 (HO-1). Furthermore, the walnut-derived peptides reduced high glucose-induced ROS overproduction and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. These results suggested that walnut-derived peptides protect HepG2 cells from high glucose-induced IR and oxidative stress by activating IRS-1/PI3 K/Akt and Nrf2/HO-1 signaling pathways. FAU - Wang, Ji AU - Wang J AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Wu, Tong AU - Wu T AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Fang, Li AU - Fang L AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Liu, Chunlei AU - Liu C AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Liu, Xiaoting AU - Liu X AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Li, Hongmei AU - Li H AUID- ORCID: 0000-0002-4852-3244 AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Shi, Junhua AU - Shi J AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Li, Meihe AU - Li M AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. FAU - Min, Weihong AU - Min W AUID- ORCID: 0000-0002-6093-2104 AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, P. R. China. minwh2000@jlau.edu.cn and National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 10 130118, P. R. China. LA - eng PT - Journal Article PL - England TA - Food Funct JT - Food & function JID - 101549033 RN - 0 (Glucose Transporter Type 4) RN - 0 (IRS1 protein, human) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Peptides) RN - 0 (Plant Extracts) RN - 0 (Protective Agents) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Glucose/*adverse effects/analysis MH - Glucose Transporter Type 4/genetics/metabolism MH - Glutathione Peroxidase/genetics/metabolism MH - Hep G2 Cells MH - Humans MH - Insulin Receptor Substrate Proteins/genetics/metabolism MH - *Insulin Resistance MH - Juglans/*chemistry MH - NF-E2-Related Factor 2/genetics/metabolism MH - Nuts/chemistry MH - Oxidative Stress/*drug effects MH - Peptides/*pharmacology MH - Plant Extracts/*pharmacology MH - Protective Agents/*pharmacology MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - Superoxide Dismutase/genetics/metabolism EDAT- 2020/08/29 06:00 MHDA- 2021/07/23 06:00 CRDT- 2020/08/29 06:00 PHST- 2020/08/29 06:00 [pubmed] PHST- 2021/07/23 06:00 [medline] PHST- 2020/08/29 06:00 [entrez] AID - 10.1039/d0fo01753a [doi] PST - ppublish SO - Food Funct. 2020 Sep 23;11(9):8112-8121. doi: 10.1039/d0fo01753a.