Spironolactone, but not Eplerenone, Impairs Glucose Tolerance in a Rat Model of Metabolic Syndrome
Spironolactone, but not Eplerenone, Impairs Glucose Tolerance in a Rat Model of Metabolic Syndrome
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DOI：
10.1292/jvms.12-0007
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发表时间：
2012-08-01
影响因子：
1.2
通讯作者：
Ikeda, Masahiro
中科院分区：
文献类型：
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作者：
Homma, Tsuyoshi;Fujisawa, Michio;Ikeda, Masahiro
虽然一些临床研究表明，螺内酯（SPL），盐皮质激素受体（MR）拮抗剂，似乎增加血糖水平，实验研究并不支持这一观点。在此，我们研究了SPL对代谢综合征动物模型SHR/NDmcr-cp（cp/cp）（ND）大鼠血糖水平的影响，并与另一种MR拮抗剂依普利酮（EPL）进行了比较。在相同剂量（100 mg/kg）下，SPL和EPL使尿钠钾比增加的程度相当，表明两种药物对ND大鼠具有相似的肾脏MR拮抗功效。有趣的是，SPL而不是EPL显著增加血糖水平。口服葡萄糖耐量试验显示SPL治疗导致葡萄糖耐受不良。血清胰岛素和脂联素的水平，血糖水平的调节剂，几乎不受SPL治疗。从另一方面来说。SPL引起血液中醛固酮水平的显著增加，已知醛固酮是胰岛素抵抗的危险因素。这些结果表明，与EPL相比。SPL在代谢综合征动物模型中的特征性损害葡萄糖耐量，与较高的血液醛固酮水平相关。
Although some clinical studies have suggested that spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, appears to increase the blood glucose levels, experimental studies have not supported this notion. Here, we investigated the effect of SPL on blood glucose levels in SHR/NDmcr-cp(cp/cp) (ND) rats, an animal model of metabolic syndrome, in comparison with that of eplerenone (EPL), another MR antagonist. At the same dose of 100 mg/kg, SPL and EPL increased the urinary sodium-to-potassium ratio to a comparable extent, indicating that both agents have similar renal MR antagonistic efficacy in ND rats. Interestingly, SPL but not EPL significantly increased the level of blood glucose. The oral glucose tolerance test revealed that treatment with SPL led to glucose intolerance. The levels of serum insulin and adiponectin, regulators of the blood glucose level, were virtually unaffected by treatment with SPL. On the other hand. SPL induced a marked increase in the blood level of aldosterone, known to be a risk factor for insulin resistance. These results demonstrate that in comparison with EPL. SPL characteristically impairs glucose tolerance in an animal model of metabolic syndrome, in association with a higher blood level of aldosterone.