Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0948265 (
metabolic syndrome
)
24,271
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed significant effects in patients with diabetes or
metabolic syndrome
(MetS) with high cardiovascular risk. Although the increased intracellular Zn
2+
level ([Zn
2+
]
i
), oxidative stress, and altered cardiac matrix metalloproteinases (MMPs) in diabetic cardiomyopathy can intersect with different signaling pathways, the exact mechanisms are not known yet. Since either MMPs or SGLT2 have important roles in cardiac-fibrosis under hyperglycemia, we aimed to examine the role of SGLT2 inhibitor dapagliflozin (DAP) on cardiac Zn
2+
-transporters responsible for [Zn
2+
]
i
-regulation, comparison to insulin (INS), together with MMP levels and systemic oxidative stress status in MetS-rats. High-carbohydrated diet-induced MetS-rats received DAP or INS for 2 weeks. DAP but not INS in MetS-rats significantly decreased high blood-glucose levels, while both treatments exerted benefits on increased total oxidative status and decreased total antioxidant status in MetS-rat plasma as well as in heart tissue. Protein levels of Zn
2+
-transporters, responsible for Zn
2+
-influx into cytosol,
ZIP7
and ZIP14 were increased with significant decrease in ZIP8 of MetS-rat cardiomyoctes, while Zn
2+
-transporters, responsible for cytosolic Zn
2+
-efflux, ZnT7 was decreased with no change in ZnT8. Both treatments induced significant beneficial effects on altered ZIP14, ZIP8, and ZnT7 levels. Furthermore, both treatments exerted benefits on depressed gelatin-zymography and protein expression levels of MMP-2 and MMP-9 in MetS-rat ventricular cardiomyocytes. The direct effect of DAP on heart was also confirmed with measurements of left ventricular developed pressure. Overall, we showed that DAP has important antioxidant-like cardio-protective effects in MetS-rats, similar to INS-effect, affecting Zn
2+
-regulation via Zn
2+
-transporters, MMPs, and oxidative stress. Therefore one can suggest that SGLT2 inhibitors can be new therapeutic agents for cardio-protection not only in hyperglycemia but also in failing heart.
...
PMID:A sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin comparison with insulin shows important effects on Zn
2+
-transporters in cardiomyocytes from insulin-resistant metabolic syndrome rats through inhibition of oxidative stress
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