Research Article Details
| Article ID: | A11731 |
| PMID: | 30773673 |
| Source: | Clin Exp Pharmacol Physiol |
| Title: | Resveratrol protects against hepatic insulin resistance in a rat's model of non-alcoholic fatty liver disease by down-regulation of GPAT-1 and DGAT2 expression and inhibition of PKC membranous translocation. |
| Abstract: | Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR). Resveratrol (RES) a potent hypolipidemic dietary polyphenol has been identified for its ability to prevent hepatic steatosis and hepatic IR in high-fat diet (HFD)-fed murine models of NAFLD. In the present study, we have carried an in vivo animal experiment to identify a novel mechanism for RES protective action. Sub-chronic (45 days) RES pretreatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser307 ) and increasing p-IRS(Tyr612 ), p-Akt(Ser473 ) and p-GSK3(Ser9 ). These effects of RES were associated with reduced expression of acyl-CoA:glycerol-sn-3-phosphate acyltransferase (GPAT-1) and diacylglycerol:acyl-CoA acyltransferase (DGAT2), two critical enzymes in the glycerol-3-phosphate pathway for de novo triglycerides synthesis. These data indicate that RES protects against NAFLD, initially, by inhibiting the early development of hepatic IR. |
| DOI: | 10.1111/1440-1681.13074 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D301 | Resveratrol | Chemical drug | DB02709 | ALOX15; ALOX5; AHR; NR1I2; NR1I3 | Anticancer agent | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |