Abstract
Aldosterone causes oxidative insults by stimulating NF‐¿B, activating‐protein (AP‐1), and c‐Jun‐N‐terminal‐kinase (JNK). In type‐2 diabetes (T2D), aldosterone‐ and hyperglycaemia‐induced oxidative events constitute a potent destructive force. We investigated the role of heme oxygenase (HO) on aldosterone/oxidative stress and insulin‐signaling in Zucker diabetic fatty rat (ZDF).HO was induced with hemin or inhibited with chromium mesoporphyrin (CrMP). Hemin reduced fasting/postprandial hyperglycaemia, while CrMP exacerbated hyperglycaemia in ZDF. The anti‐diabetic effect was accompanied by enhanced HO activity, catalase, bilirubin, ferritin and total anti‐oxidant capacity, whereas reduced aldosterone, 8‐isoprostane, JNK, NF‐¿B, AP‐1 and AP‐2 were observed. Interestingly, hemin increased insulin levels alongside cAMP and cGMP, two secondary‐messengers that also regulate insulin release. Furthermore, agents that promote insulin‐signaling including adiponectin, AMPK, aldolase‐B and GLUT4, were robustly increased. Correspondingly, hemin reduced glucose/insulin tolerance, lowered insulin resistance (HOMA‐IR), and reversed the inability of insulin to enhance GLUT4.The suppression of hyperglycaemia‐ and aldosterone‐induced oxidative stress alongside the potentiation of insulin‐sensitizing pathways may account anti‐diabetic effect.
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