Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of obesity, cardiometabolic syndrome (CMS), and type 2 diabetes mellitus (DM2), as well as their devastating cardiovascular consequences, keep rising with increasing human and economical costs. For a long time, insulin resistance has been the main player in the pathogenesis and treatment of DM2, but every day more knowledge is gained about the central role of beta-cell failure, not only in the appearance of hyperglycemia but also in the failure of the pharmacological therapy. beta-Cell failure implies impairment of glucosestimulated insulin secretion and loss of beta-cell mass. Hyperglycemia, elevated circulating fatty acids, inadequate local activation of renin angiotensin system, and chronic low grade inflammation are conditions that coexist in the CMS and DM2 that turn out to be deleterious for the beta-cell functioning and existance. Excessive oxidative stress secondary to increased production of reactive oxygen species and decreased availability of antioxidants is a possible common converging point of the multiple noxious stimuli. Activation of the NADPH oxidase complex secondary to angiotensin II stimulation is of interest, as its pharmacological blockade has beneficial effects. New knowledge about the intimate mechanisms of oxidative-stress induced beta-cell failure will provide new therapeutic targets against CMS and DM2.
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PMID:The expanding role of oxidative stress, renin angiotensin system, and beta-cell dysfunction in the cardiometabolic syndrome and Type 2 diabetes mellitus. 1750 16

Type 2 diabetes mellitus (DM2) and obesity are major risk factors for erectile dysfunction (ED). In diabetes, increased oxidative stress leads to decreased nitric oxide (NO) bioavailability, and diabetic patients appear to be less responsive to conventional therapy with phosphodiesterase type 5 inhibitors. We investigated whether the soluble guanylyl cyclase stimulator BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4ylamine) is effective in improving impaired corpus cavernosum (CC) relaxation in obese DM2 mice by reducing oxidative stress. Adult db/db(-/-) mice or their lean db(/+) littermates were used to assess vascular function, cGMP levels, antioxidant status, NADPH oxidase expression, and superoxide formation in the absence or presence of BAY 41-2272. Results showed that BAY 41-2272 (10(-8) to 10(-5) M) potently relaxed CC from db(/+) or db/db(-/-) mice in a similar manner. BAY 41-2272 significantly enhanced both endothelium-dependent and nitrergic relaxation induced by electrical field stimulation (EFS), and improved the impaired relaxation to acetylcholine and EFS in the diabetic animals in a concentration-dependent manner (10(-8) to 10(-7) M). BAY 41-2272 increased cGMP levels and potentiated relaxation responses to exogenous NO in CC. Total antioxidant status was reduced in plasma and urine whereas expression of vascular NADPH oxidase subunits (gp91phox, p22phox, and p47phox) was increased in the CC of db/db(-/-) mice, suggesting a state of oxidative stress. These effects were prevented by BAY 41-2272 in a concentration-dependent manner. These results suggest that BAY 41-2272 improves CC relaxation in db/db(-/-) mice by increasing cGMP and augmenting antioxidant status, making this drug is a potential novel candidate to treat ED.
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PMID:Beneficial effect of the soluble guanylyl cyclase stimulator BAY 41-2272 on impaired penile erection in db/db-/- type II diabetic and obese mice. 2574 Aug 97