Research Article Details
| Article ID: | A23356 |
| PMID: | 23845075 |
| Source: | Curr Diabetes Rev |
| Title: | The influence of diabetes in the pathogenesis and the clinical course of hepatocellular carcinoma: recent findings and new perspectives. |
| Abstract: | Up to 50% of patients with hepatocellular carcinoma (HCC) have the so-called "cryptogenic cirrhosis." Most of them are affected by at least one of the condition characterizing the metabolic syndrome, as obesity or diabetes. Recent observations found that type-2 diabetes mellitus (DM) confers a three-fold risk of HCC. Main molecular feature of the conditions of metabolic syndrome is insulin resistance, i.e. the reduced sensitivity to insulin action and, as consequence, increased secretion of this hormone. Insulin resistance and hyperinsulinemia influence hepatocarcinogenesis via several molecular pathways, such as phosphatase and tensin homolog (PTEN)/P13K/Akt and MAPK kinase (MAPKK). Diabetes also seems to influence negatively the prognosis and the clinical course of HCC patients, independently from the cause of the underlying cirrhosis. It's well known that insulin-sensitizing drugs may reduce the incidence of HCC. Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell. Also thiazolidinediones seem to prevent tumor formation in the liver via the inhibition of peroxisome proliferator-activated receptor gamma-independent regulation of nucleophosmin. More debated is the role of sulfonylureas in decreasing HCC incidence in diabetic patients. Further investigations are needed to define reliable indications to therapy and surveillance in patients with diabetes or insulin resistance. |
| DOI: | 10.2174/15733998113099990068 |
| 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 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D225 | Metformin | Chemical drug | DB00331 | PRKAB1 inducer activator; ETEDH inhibitor; GPD1 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D353 | Sulfonylurea | Chemical drug | -- | -- | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D612 | Rapamycin | Miscellany | -- | Immunosuppressants; Methylmalonyl CoA mutase stimulants; MTOR protein inhibitors; T lymphocyte inhibitors | -- | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D157 | Glucophage | Chemical drug | DB00331 | -- | -- | Under clinical trials | Details |