Urolithin A activates autophagy to improve liver insulin resistance in diabetic mice / 中草药
Chinese Traditional and Herbal Drugs
;
(24): 710-716, 2020.
Artículo
en Chino
| WPRIM
| ID: wpr-846633
ABSTRACT
Objective:
To investigate the effect of urolithin A (UA) on liver insulin signaling pathway in type 2 diabetes model mice and its relationship with autophagy.Methods:
C57BL/6 mice were randomly divided into four groups according to body weight, namely control group, model group, UA (50 mg/kg) group, UA (50 mg/kg) combined with chloroquine (50 mg/kg) group. After 6 weeks of high-fat diet, a type 2 diabetes model was established by ip streptozotocin (STZ). The mice in each group were ig administrated for 7 weeks, and their body weight, water intake, blood lipids, fasting blood glucose (FBG), and fasting insulin (FINS) levels were measured; HE staining was used to observe pathological changes in mouse liver tissue; Western blotting was used to detect mouse phosphorylated protein kinase B (p-Akt), glucose transporter 2 (Glut2), phosphorylated glycogen synthase kinase-3β(p-GSK3β) and autophagy-related protein microtubule-related protein 1 light chain 3 II/I (LC3II/I) and selective autophagy linker protein (p62) expression levels.Results:
Compared with the model group, UA significantly improved liver tissue steatosis and edema in diabetic model mice, significantly reduced plasma triacylglycerol, free fatty acids, low-density lipoprotein-cholesterol, FBG, FINS levels, and increased high-density lipoprotein-cholesterol level (P < 0.01); UA significantly reduced HOMA-IR and increased ISI (P < 0.01), up-regulated the protein expression of p-Akt, Glut2, p-GSK3β, and LC3II/I in liver tissues, and inhibited the expression of p62 protein (P < 0.01). Combined with chloroquine, FBG, FINS, and HOMA-IR in mice were increased, and ISI was decreased (P < 0.05); Liver tissue edema and steatosis were significantly aggravated; The expression levels of p-Akt, Glut2, LC3II/I protein in liver tissue were decreased, and p62 protein expression levels were increased (P < 0.05), indicating that the autophagy inhibitor chloroquine significantly weakened the effect of UA.Conclusion:
UA may improve liver insulin resistance in diabetic mice by activating liver autophagy.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
Chinese Traditional and Herbal Drugs
Año:
2020
Tipo del documento:
Artículo
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