Research Article Details
| Article ID: | A26682 |
| PMID: | 19958640 |
| Source: | Zhonghua Gan Zang Bing Za Zhi |
| Title: | [Role of JNK signal transduction pathway in nonalcoholic fatty liver disease]. |
| Abstract: | OBJECTIVE: To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the rats of nonalcoholic fatty liver disease (NAFLD). METHODS: Sixty four Sprague-Dawley rats were randomly divided into four groups: 8-week control group (NG8w), 12-week control group (NG12 w), 8-week high-fat diet (HG8w), and 12-week high-fat diet group (HG12w), with 16 rats in each group. Glucose infusion rate (GIR) was tested by euglycemic hyperinsulinemic clamp; aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), free fatty acid (FFAs), fast insulin (FIns), tumor necrosis factor alpha (TNF alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemistry automatic analyzer or RIA; The expression of JNK1, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 Ser307 (p-IRS-1 Ser307), Protein kinase B (PKB) and phospho-PKB Ser473 (p- PKB Ser473) were detected by Western blot. RESULTS: Compared to control group, body weight, liver index, serum levels of ALT, AST, TG, TC, FIns, FFAs, TNF alpha, and TC, TG FFAs, MDA in liver homogenates were increased, while the level of SOD, and GIR were decreased. The expression of JNK1 protein and p-IRS-1 Ser307 in liver tissue was up-regulated, while expression of p-PKB Ser473 was decreased (P < 0.05). A positive correlation was found between the expression intensity of JNK1 and IR (Pearson correlation: 0.718, P < 0.01). CONCLUSION: The high-fat could induce the expression of JNK1, which in turn modulates the phosphorylation of proteins in the insulin signaling pathway, and induces insulin resistant. |
| DOI: |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |