Research Article Details
| Article ID: | A11544 |
| PMID: | 30850262 |
| Source: | Trends Endocrinol Metab |
| Title: | Calcium Signaling As a Therapeutic Target for Liver Steatosis. |
| Abstract: | Hepatic steatosis, the first step in nonalcoholic fatty liver disease (NAFLD), can arise from various pathophysiological conditions. While lipid metabolism in the liver is normally balanced such that there is no excessive lipid accumulation, when this homeostasis is disrupted lipid droplets (LDs) accumulate in hepatocytes resulting in cellular toxicity. The mechanisms underlying this accumulation and the subsequent hepatocellular damage are multifactorial and poorly understood, with the result that there are no currently approved treatments for NAFLD. Impaired calcium signaling has recently been identified as a cause of increased endoplasmic reticulum (ER) stress contributing to hepatic lipid accumulation. This review highlights new findings on the role of impaired Ca2+ signaling in the development of steatosis and discusses potential new approaches to NAFLD treatment based on these new insights. |
| DOI: | 10.1016/j.tem.2019.02.005 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D055 | Calcium | Chemical drug | DB01373 | CAST; COMP; CP; BMP4; MGP | -- | Under clinical trials | Details |