Research Article Details
| Article ID: | A07382 |
| PMID: | 32519009 |
| Source: | Curr Diab Rep |
| Title: | Purine Metabolite Signatures and Type 2 Diabetes: Innocent Bystanders or Actionable Items? |
| Abstract: | PURPOSE OF REVIEW: This article reviews evidence linking cardiometabolic conditions with changes in purine metabolites, including increased serum uric acid (sUA), and discusses intervention studies that investigated the therapeutic relevance of these associations. RECENT FINDINGS: Metabolic and epidemiological findings support a correlation between sUA and circulating levels of other purines with insulin resistance (IR) and risk factors for cardiovascular disease (CVD). In addition, increased activity of xanthine oxidoreductase (XOR), the rate-limiting enzyme for UA production, has been detected in tissues targeted by obesity. Yet, inhibition of XOR in pre-clinical and clinical studies generally failed to support a causal role for excess sUA in IR and CVD. The lack of efficacy of XOR inhibitors strongly suggests that UA is a marker of, rather than a direct contributory factor for, cardiometabolic diseases. Validation of the function of other purines will require a paradigm shift, from a "UA-centric" view to a more granular assessment of the entire purine network and its interaction with other pathways. |
| DOI: | 10.1007/s11892-020-01313-z |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D006 | Allopurinol | Chemical drug | DB00437 | XO inhibitor | -- | Under clinical trials | Details |