Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL via the Wnt3a/ß-Catenin/GSK-3ß Pathway in a Type 2 Diabetes Mellitus Model.
J Agric Food Chem
; 72(29): 16204-16220, 2024 Jul 24.
Article
de En
| MEDLINE
| ID: mdl-38984968
ABSTRACT
The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/ß-Catenin/GSK-3ß pathway in glucose-induced insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status via the Wnt3a/ß-Catenin/GSK-3ß pathway.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Neuroprotecteurs
/
Juglans
/
Diabète de type 2
/
Bêta-Caténine
/
Protéine Wnt3A
/
Glycogen synthase kinase 3 beta
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
J Agric Food Chem
Année:
2024
Type de document:
Article
Pays de publication:
États-Unis d'Amérique