Research Article Details
| Article ID: | A13257 |
| PMID: | 30060948 |
| Source: | Biochem Biophys Res Commun |
| Title: | Saxagliptin regulates M1/M2 macrophage polarization via CaMKKβ/AMPK pathway to attenuate NAFLD. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic disease, is an important complication of diabetes mellitus (DM). Inflammation plays a crucial role in the development and progression of NAFLD. Moreover, the pathological formation of NAFLD is closely related to accumulation and polarization of hepatic macrophages. Saxagliptin, a newly antidiabetic agent, can suppress hepatic inflammation reportedly. However, underlying mechanisms remain poorly explored. In this study, we showed saxagliptin alleviated lipid accumulation and attenuated liver inflammation with downregulation of inflammation factors in diabetic rats. Moreover, saxagliptin could reduce the phenotype of M1 macrophage iNOS and increase the phenotype of M2 macrophage CD206. We also found saxagliptin increased CaMKKβ/AMPK activation. In vitro, human THP-1 monocytes were differentiated into M1/M2 macrophages by LPS/IL-4. We clarified saxagliptin's anti-inflammatory effect by reducing NF-κB, TNF-α expression and promoting M2 macrophage polarization. Furthermore, we demonstrated CaMKKβ-dependent AMPK activation was involved in macrophage polarization. In conclude, our results detected saxagliptin could attenuated inflammation through regulation of M1/M2 macrophage polarization and might be via CaMKKβ/AMPK pathway. |
| DOI: | 10.1016/j.bbrc.2018.07.090 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | 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 | |
|---|---|---|---|---|---|---|---|
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |