Research Article Details
| Article ID: | A27544 |
| PMID: | 18094066 |
| Source: | Am J Physiol Regul Integr Comp Physiol |
| Title: | Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. |
| Abstract: | The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney disease (CKD), has become a growing worldwide health problem. Insulin resistance is a key factor for the development of the CMS and is strongly related to obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and NAFLD. Insulin resistance in skeletal muscle is particularly important since it is normally responsible for more than 75% of all insulin-mediated glucose disposal. However, the molecular mechanisms responsible for skeletal muscle insulin resistance remain poorly defined. Accumulating evidence indicates that low-grade chronic inflammation and oxidative stress play fundamental roles in the development of insulin resistance, and inflammatory cytokines likely contribute to the link between inflammation, oxidative stress, and skeletal muscle insulin resistance. Understanding the mechanisms by which skeletal muscle tissue develops resistance to insulin will provide attractive targets for interventions, which may ultimately curb this serious problem. This review is focused on the effects of inflammatory cytokines and oxidative stress on insulin signaling in skeletal muscle and consequent development of insulin resistance. |
| DOI: | 10.1152/ajpregu.00561.2007 |
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|---|
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| 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 |