Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid
Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid
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DOI：
10.1080/13813455.2018.1509220
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发表时间：
2020-05-26
影响因子：
3
通讯作者：
Olatunji, L. A.
中科院分区：
文献类型：
--
作者：
Adeyanju, O. A.;Michael, O. S.;Olatunji, L. A.
Context:Estrogen-progestin combined oral contraceptive (COC) has been connected to mineralocorticoid receptor (MR) activation and adverse cardiometabolic events. We consequently hypothesised that insulin resistance (IR), hyperuricemia, and elevated circulating GSK-3 induced by COC is through activation of MR via mineralocorticoid and glucocorticoid pathways. Methods:Female Wistar rats aged 12 weeks received (po) vehicle and COC (1.0 mu g ethinylestradiol plus 5.0 mu g levonorgestrel) with or without MR blocker (0.25 mg/kg spironolactone; Spl), daily for eight weeks. Results:Data showed that COC treatment led to increased IR, 1-hour postload glucose level, insulinemia, triglyceride/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol ratio, uric acid, GSK-3, aldosterone, corticosterone values, impaired glucose tolerance and pancreatic beta-cell function. However, MR blockade by Spl ameliorated all these alterations except that of aldosterone. Conclusion:The results demonstrate that COC induces IR, hyperuricemia and high GSK-3 levels through activation of MR via glucocorticoid dependent pathway.
