Research Article Details
| Article ID: | A12942 |
| PMID: | 30214535 |
| Source: | Exp Ther Med |
| Title: | Sitagliptin reduces insulin resistance and improves rat liver steatosis via the SIRT1/AMPKα pathway. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. It is asymptomatic at presentation and is frequently identified among individuals with metabolic dysfunction, including obesity and diabetes. NAFLD is primarily characterized by the accumulation of triacylglycerol in the liver. Since insulin resistance and fat metabolism dysregulation are major causes of type 2 diabetes and NAFLD, anti-diabetes agents are widely considered as potential therapy strategies for NAFLD. Sitagliptin, an inhibitor of dipeptidyl peptidase-4, has been developed as an oral anti-hyperglycemic agent. In the present study, the effect of sitagliptin on the progression of NAFLD was evaluated in a rat model fed with a high fat diet (HFD). It was identified that sitagliptin significantly suppressed lipid accumulation in rat blood and liver and improved insulin resistance. Furthermore, it was revealed that sitagliptin reactivated the HFD-suppressed SIRT1/AMPK axis pathway and upregulated its downstream target genes, modulating fatty acid metabolism. These findings demonstrate a preventive effect of sitagliptin on hepatic lipid dysregulation and suggest that sitagliptin has potential as a clinical therapeutic strategy for NAFLD. |
| DOI: | 10.3892/etm.2018.6554 |
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D338 | Sitagliptin | Chemical drug | DB01261 | DPP4 inhibitor | Antidiabetic drug | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |