PMID- 36802594 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20230307 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 71 IP - 8 DP - 2023 Mar 1 TI - Walnut-Derived Peptides Promote Autophagy via the Activation of AMPK/mTOR/ULK1 Pathway to Ameliorate Hyperglycemia in Type 2 Diabetic Mice. PG - 3751-3765 LID - 10.1021/acs.jafc.2c07112 [doi] AB - Autophagy flux plays a significant protective role in type 2 diabetes mellitus (T2DM). However, the mechanisms by which autophagy mediates insulin resistance (IR) to ameliorate T2DM remain unclear. This study explored the hypoglycemic effects and mechanisms of walnut-derived peptides (fraction 3-10 kDa and LP5) in streptozotocin and high-fat-diet-induced T2DM mice. Findings revealed that walnut-derived peptides reduced the levels of blood glucose and FINS and ameliorated IR and dyslipidemia. They also increased SOD and GSH-P(X) activities and inhibited the secretion of TNF-alpha, IL-6, and IL-1beta. Additionally, they increased the levels of ATP, COX, SDH, and MMP of liver mitochondria. Western blotting indicated that walnut-derived peptides up-regulated LC3-II/LC3-I and Beclin-1 expression, while they down-regulated p62 expression, which may be associated with the activation of the AMPK/mTOR/ULK1 pathway. Finally, the AMPK activator (AICAR) and inhibitor (Compound C) were used to verify that LP5 could activate autophagy through the AMPK/mTOR/ULK1 pathway in IR HepG2 cells. FAU - Hou, Weiyu AU - Hou W AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Zhao, Fanrui AU - Zhao F AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Fang, Li AU - Fang L AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Wang, Xiyan AU - Wang X AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Wu, Dan AU - Wu D AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Liu, Chunlei AU - Liu C AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Leng, Yue AU - Leng Y AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Gao, Yawen AU - Gao Y AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Fu, Junxi AU - Fu J AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Wang, Ji AU - Wang J AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. FAU - Min, Weihong AU - Min W AUID- ORCID: 0000-0002-6093-2104 AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, People's Republic of China. AD - National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, People's Republic of China. LA - eng PT - Journal Article DEP - 20230219 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - 0 (Peptides) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 0 (Plant Proteins) RN - EC 2.7.11.1 (Ulk1 protein, mouse) SB - IM MH - Animals MH - Mice MH - AMP-Activated Protein Kinases/genetics/metabolism MH - Autophagy MH - *Diabetes Mellitus, Experimental/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hyperglycemia/drug therapy MH - *Juglans/metabolism MH - Peptides/pharmacology MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Plant Proteins/pharmacology MH - Signal Transduction OTO - NOTNLM OT - AMPK/mTOR/ULK1 OT - autophagy OT - insulin resistance OT - type 2 diabetes mellitus OT - walnut-derived peptides EDAT- 2023/02/22 06:00 MHDA- 2023/03/03 06:00 CRDT- 2023/02/21 17:21 PHST- 2023/02/22 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/21 17:21 [entrez] AID - 10.1021/acs.jafc.2c07112 [doi] PST - ppublish SO - J Agric Food Chem. 2023 Mar 1;71(8):3751-3765. doi: 10.1021/acs.jafc.2c07112. Epub 2023 Feb 19.