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Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UMLS:C0948265 (
metabolic syndrome
)
24,271
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Polycystic ovary syndrome (PCOS) is associated with infertility, increased androgen levels, and insulin resistance. In adipose tissue, zinc facilitates insulin signaling. Circulating zinc levels are altered in obesity, diabetes, and PCOS; and zinc supplementation can ameliorate metabolic disturbances in PCOS. In adipose tissue, expression of zinc influx transporter
ZIP14
varies with body mass index (BMI), clinical markers of
metabolic syndrome
, and
peroxisome proliferator-activated receptor gamma
(
PPARG
). In this study, we investigated expression levels of
ZIP14
and
PPARG
in subcutaneous adipose tissue of 36 PCOS women (17 lean and 19 obese women) compared with 23 healthy controls (7 lean and 16 obese women). Further, expression levels of zinc transporter
ZIP9
, a recently identified androgen receptor, and zinc efflux transporter
ZNT1
were investigated, alongside lipid profile and markers of glucose metabolism [insulin degrading enzyme, retinol-binding protein 4 (
RBP4
), and glucose transporter 4 (
GLUT4
)]. We find that
ZIP14
expression is reduced in obesity and positively correlates with
PPARG
expression, which is downregulated with increasing BMI.
ZNT1
is upregulated in obesity, and both
ZIP14
and
ZNT1
expression significantly correlates with clinical markers of altered glucose metabolism. In addition,
RBP4
and
GLUT4
associate with obesity, but an association with PCOS as such was present only for
PPARG
and
RBP4
.
ZIP14
and
ZNT1
does not relate to clinical androgen status and
ZIP9
is unaffected by all parameters investigated. In conclusion, our findings support the existence of a zinc dyshomeostasis in adipose tissue in metabolic disturbances including PCOS-related obesity.
...
PMID:Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters
ZIP14
and
ZNT1
in Obesity and Polycystic Ovary Syndrome. 2830 17
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
1
. 3044 46
