Research Article Details
| Article ID: | A15859 |
| PMID: | 28678199 |
| Source: | Int J Mol Sci |
| Title: | The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver. |
| Abstract: | Adult growth hormone deficiency (GHD) is characterized by metabolic abnormalities associated with visceral obesity, impaired quality of life, and increased mortality. Patients with adult GHD show increased prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), and growth hormone (GH) replacement therapy has been shown to improve these conditions. It has also been demonstrated that a decrease in the GH insulin-like growth factor-I (IGF-I) axis is closely associated with the progression of general NAFLD, suggesting a physiological role of these hormones for the maintenance of the liver. NASH histologically demonstrates inflammation, necrosis, and fibrosis, in addition to steatosis (and is a serious disease because it can progress to liver cirrhosis and hepatocellular carcinoma in a subset of cases). While fibrosis determines the prognosis of the patient, efficacious treatment for fibrosis is crucial; however, it has not yet been established. Recent studies have clarified the essential roles of GH and IGF-I in the liver. GH profoundly reduces visceral fat, which plays an important role in the development of NAFLD. Furthermore, GH directly reduces lipogenesis in the hepatocytes. IGF-I induces cellular senescence and inactivates hepatic stellate cells, therefore ameliorating fibrosis. IGF-I treatment has been shown to improve animal models of NASH and cirrhosis, suggesting potential clinical applications of IGF-I in these conditions. In this review, I will focus on the important roles of GH and IGF-I in the liver, their underlying mechanisms, and their potential therapeutic applications. |
| DOI: | 10.3390/ijms18071447 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D160 | Growth Hormone | Biological drug | DB00052 | GHR ligand; PRLR ligand | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D343 | Somatropin | Biological drug | DB00052 | GHR ligand; PRLR ligand | Hormone replacement drug | Under clinical trials | Details |
| D602 | IGF-I | Miscellany | -- | P53 activitor | Anti-fibrosis | Under investigation | Details |