Research Article Details
| Article ID: | A14156 |
| PMID: | 29560693 |
| Source: | Acta Gastroenterol Belg |
| Title: | Apoptosis and Disease Severity is Associated with Insulin Resistance in Non-alcoholic Fatty Liver Disease. |
| Abstract: | BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods. RESULTS: HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively). CONCLUSION: This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression. |
| DOI: |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |