Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid.

O A Adeyanju, O S Michael, A O Soladoye, L A Olatunji

Archives of physiology and biochemistry 2020 Jul

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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 μg ethinylestradiol plus 5.0 μg 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 β-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.

Citation

O A Adeyanju, O S Michael, A O Soladoye, L A Olatunji. Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid. Archives of physiology and biochemistry. 2020 Jul;126(3):225-234