High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes.

High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes.
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高葡萄糖通过新生大鼠心肌细胞中的 I 型盐皮质激素受体刺激醛固酮诱导的肥大。

DOI:
10.1210/endo.137.10.8828470
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发表时间:
1996
期刊:
影响因子:
4.8
通讯作者:
J. Funder
J. Funder
中科院分区:
医学2区
文献类型:
--
作者:
A. Sato;J. Funder

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先前的研究表明,醛固酮加盐负荷在体内引起大鼠心脏肥厚,而在体外,醛固酮和葡萄糖均刺激成纤维细胞生长。本研究考察了肾上腺类固醇通过矿化皮质激素和糖皮质激素受体(MR和GR)对培养新生大鼠心肌细胞[3H]亮氨酸掺入的影响,以及葡萄糖升高在调节这种影响中的作用。皮质酮、高选择性II型(糖皮质激素)受体激动剂RU28362或高剂量醛固酮可降低GR的掺入;当这种作用被糖皮质激素拮抗剂RU486阻断时,醛固酮(而非皮质酮)显著提高亮氨酸的掺入,这表明mr通过高糖单独孵育不会增加亮氨酸的掺入,但在阈值和最大反应方面显著增加醛固酮的增厚作用。葡萄糖-醛固酮的协同作用是通过MR进行的,完全被螺内酯阻断。醛固酮单独作用或与葡萄糖升高一起作用时,增加掺入的时间过程是相同的,这与广泛的转录效应一致,表明高葡萄糖的作用不是速率限制。葡萄糖效应既不反映MR合成的诱导,也不反映其亲和力的增加;它是特异性的,因为它不会被相同浓度的l -葡萄糖或甘露醇模仿,并且通过蛋白激酶C活性的增加来介导,可以在可溶性和颗粒室中测量。这种协同作用在糖尿病心脏后遗症中的作用仍有待探讨。
Previous studies have shown that aldosterone plus salt loading cause cardiac hypertrophy in rats in vivo, and that in vitro, both aldosterone and glucose stimulate fibroblast growth. The present studies examined the effects of adrenal steroids via mineralocorticoid and glucocorticoid receptors (MR and GR) on [3H]leucine incorporation by neonatal rat cardiomyocytes in culture and the role of elevated glucose in modulating such effects. GR occupancy by corticosterone, the highly selective type II (glucocorticoid) receptor agonist RU28362, or high doses of aldosterone lowers incorporation; when this effect is blocked by coincubation with the glucocorticoid antagonist RU486, aldosterone, but not corticosterone, markedly elevates leucine incorporation, indicating a specific mineralocorticoid effect via MR. Incubation with high glucose alone does not increase incorporation, but markedly increases the hypertropic effect of aldosterone in terms of both threshold and maximum response. The glucose-aldosterone synergy is via MR and is completely blocked by spironolactone. The time course of increased incorporation is identical for aldosterone acting alone or with elevated glucose, consistent with widespread transcriptional effects and suggesting that the contribution of high glucose is not rate limiting. The glucose effect reflects neither induction of MR synthesis nor an increase in their affinity; it is specific, in that it is not mimicked by L-glucose or mannitol at equal concentrations, and is mediated via an increase in protein kinase C activity that can be measured in both soluble and particulate compartments. The role of this synergy in the cardiac sequelae of diabetes remains to be explored.
糖皮质激素受体在培养的集合管细胞中介导盐皮质激素样作用。
DOI: 10.1152/ajprenal.1990.259.4.f672
发表时间: 1990
期刊: The American journal of physiology
影响因子: --
作者:
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通讯作者: Fejes-Toth,G
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DOI: 10.1172/jci116079
发表时间: 1992
期刊: The Journal of clinical investigation
影响因子: --
作者:
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通讯作者: Schrier,RW
DOI: 10.1172/jci117275
发表时间: 1994-06-01
影响因子: 15.9
作者:
WILLIAMS, B;HOWARD, RL
通讯作者: HOWARD, RL
DOI: 10.1152/ajpendo.1990.258.3.e482
发表时间: 1990-03-01
影响因子: --
作者:
GOMEZSANCHEZ, EP;FORT, CM;GOMEZSANCHEZ, CE
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葡萄糖引起的血管平滑肌功能障碍:蛋白激酶 C 的作用。
DOI: 10.1097/00004872-199505000-00001
发表时间: 1995
影响因子: 4.9
作者:
Williams,B
通讯作者: Williams,B