Research Article Details
| Article ID: | A06309 |
| PMID: | 32933722 |
| Source: | Tissue Cell |
| Title: | Liraglutide in combination with human umbilical cord mesenchymal stem cell could improve liver lesions by modulating TLR4/NF-kB inflammatory pathway and oxidative stress in T2DM/NAFLD rats. |
| Abstract: | Studies have shown that liraglutide, or human umbilical cord mesenchymal stem cell (hUC-MSCs) can improve non-alcoholic fatty liver disease (NAFLD). However there have been no studies on the combination of the two used to treat NAFLD. This study aimed to explore the therapeutic effects of combination of liraglutide and hUC-MSCs on liver injury in rats with type 2 diabetes mellitus (T2DM) and NAFLD, and further investigate their mechanisms. Sprague Dawley rats fed by a high fat and high sucrose diet were randomly divided into 5 groups, including NC group, T2DM/NAFLD group, liraglutide group (treated with liraglutide, 200 μg/kg, twice daily for 8 weeks), hUC-MSCs group (treated with hUC-MSCs at the first and fifth weeks), liraglutid＋hUC-MSCs group (treated with liraglutide and hUC-MSCs). Liver tissue was procured for histological examination, real-time qRT-PCR and Western blot analysis. After treatment, liraglutide and hUC-MSCs reduced serum ALT and AST levels, alleviate liver inflammation and improved liver histopathology. The expressions of inflammatory cytokines, TLR4 and NF-κB in serum and liver were significantly inhibited, particularly in the combination treatment group. Eight weeks after liraglutide or hUC-MSCs administration, FBG, HbA1c, HOMA-IR, ALT, AST, Liver wet eight and hepatic TLR4, NF-κB, IL-6, TNF-α, 8-OHdG mRNA and proteins were significantly decreased, and the levels of SOD expression were significantly increased in three treatment groups compared with T2DM/NAFLD group. This study suggests that liraglutide in combination with hUC-MSCs could significantly improve glycolipid metabolism, insulin resistance and liver injury in T2DM/NAFLD rats. Its mechanism may be related to the down-regulation of the TLR4/NF-κB inflammatory pathway and improvement in oxidative stress. |
| DOI: | 10.1016/j.tice.2020.101382 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| S15 | Cell therapy | Mesenchymal stem cells; Stem cell therapy | -- | -- | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D207 | Liraglutide | Biological drug | DB06655 | GLP1R activator; GLP1R agonist; GCG receptor antagonist activity | Improve insulin resistance | Under clinical trials | Details |