Research Article Details
| Article ID: | A07629 |
| PMID: | 32414752 |
| Source: | BMJ Open Gastroenterol |
| Title: | Spatial expression of glucagon-like peptide 1 receptor and caveolin-1 in hepatocytes with macrovesicular steatosis in non-alcoholic steatohepatitis. |
| Abstract: | OBJECTIVE: Non-alcoholic steatohepatitis (NASH) can progress to fibrosis, cirrhosis and end-stage liver disease. Glucagon-like peptide 1 receptor (GLP-1R) mediates β cell function. Its receptor agonists, currently used to treat type 2 diabetes mellitus, might be effective against NASH. GLP-1R, a G protein-coupled receptor family member, preferentially localises to caveolae. Therefore, we ascertained the cellular localisation of GLP-1R and caveolin (CAV)-1 in NASH liver. METHODS: Liver biopsies were obtained from three patients with NASH and were compared with those of four normal patients. Immunohistochemistry (IHC) and immunoelectron microscopy (IEM) were used to compare GLP-1R and CAV-1 expression in the livers of patients with metastatic liver cancer and normal patients. RESULTS: IHC showed that GLP-1R localised to basolateral membranes of hepatocytes with macrovesicular steatosis and was expressed in monocytes infiltrating hepatic sinusoids. CAV-1 was minimally associated with low-electron density lipid droplets (LDs) in hepatocytes. IEM showed small clusters of GLP-1R molecules on the peripheral rims of LDs and on cytoplasmic leaflets of endoplasmic reticulum membranes and vesicles, whereas CAV-1 molecules were found in LD caveolae. CONCLUSIONS: GLP-1R is present in the lipid microdomains of hepatocytes with macrovesicular steatosis. These results may help inform future studies about the liver-specific mechanisms of GLP-1 modulation in NASH therapy. |
| DOI: | 10.1136/bmjgast-2019-000370 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | 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 |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |