Research Article Details
| Article ID: | A26791 |
| PMID: | 19779336 |
| Source: | Curr Opin Lipidol |
| Title: | Thiazolidinediones and the liver in humans. |
| Abstract: | PURPOSE OF REVIEW: To review recent advances in the understanding of the mechanism of action of thiazolidinediones (TZDs) in humans. RECENT FINDINGS: The liver is characterized by excess fat accumulation due to nonalcoholic causes (non-alcoholic fatty liver disease) in most patients with the metabolic syndrome and type 2 diabetes. Simple steatosis can progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. Both of the commercially available antihyperglycemic TZD agonists, pioglitazone and rosiglitazone, are markedly effective in reducing liver fat content by 30-50% and sensitizing the liver to insulin. This reduces the amount of endogenous and exogenous insulin needed to inhibit hepatic glucose production. Decreases in liver fat are closely correlated with increases in serum adiponectin, which is an insulin-sensitizing adipokine produced exclusively by adipose tissue. Both TZDs are equally effective in reducing liver fat. Regarding lipid metabolism, enhanced hepatic insulin sensitivity would be predicted to lower VLDL and serum triglycerides and increase HDL-cholesterol. Pioglitazone and rosiglitazone have different effects on serum lipids, which cannot be attributed to simple insulin sensitization. Very recently, TZDs have been shown to reduce not only steatosis but possibly also hepatocellular damage in NASH. SUMMARY: Given the uncertainties in benefits of TZDs in reducing cardiovascular disease in type 2 diabetes, as well as other side-effects (heart failure, fractures), TZDs may in the future be increasingly used in patients with nonalcoholic steatohepatitis. |
| DOI: | 10.1097/MOL.0b013e3283321d37 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| 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 |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D311 | Rosiglitazone | Chemical drug | DB00412 | PPARG agonist; PPARA; PPARD | Improve insulin resistance | Failed in clinical trials | Details |