Moisés Regina S, Carvalho Carla R O, Shiota Debora, Saad Mario J A
Disciplina de Endocrinologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
Metabolism. 2003 Mar;52(3):273-8. doi: 10.1053/meta.2003.50044.
Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been reported to improve insulin sensitivity. However, despite extensive investigation, the mechanisms responsible for this effect are not fully understood. Reduction of plasma angiotensin II and inhibition of kininase II have been suggested to contribute to improve insulin sensitivity. Insulin binding was measured at tracer insulin concentration in intact cells with or without captopril treatment. Specific binding, expressed as percent of total insulin added, was not different in control and captopril-treated cells. However, captopril treatment caused an increase in insulin-induced insulin receptor substrate-1 (IRS-1) phosphorylation accompanied by an increased association of IRS-1 with phosphoinositide-3 kinase (PI-3 kinase), despite no change on insulin receptor (IR) autophosphorylation. There was also an increased threonine kinase B (AKT) phosphorylation in captopril-treated cells followed by enhanced basal and insulin-stimulated glucose uptake. These results indicate that captopril treatment has a direct effect on early phosphorylation events induced by insulin in BC3H-1 myocytes.
卡托普利是一种血管紧张素转换酶（ACE）抑制剂，据报道它能改善胰岛素敏感性。然而，尽管进行了广泛研究，但其产生这种作用的机制尚未完全明确。血浆血管紧张素II的减少和激肽酶II的抑制被认为有助于改善胰岛素敏感性。在有或无卡托普利处理的完整细胞中，以示踪胰岛素浓度测量胰岛素结合情况。以添加的总胰岛素的百分比表示的特异性结合，在对照细胞和卡托普利处理的细胞中并无差异。然而，尽管胰岛素受体（IR）自身磷酸化没有变化，但卡托普利处理导致胰岛素诱导的胰岛素受体底物-1（IRS-1）磷酸化增加，同时IRS-1与磷脂酰肌醇-3激酶（PI-3激酶）的结合增加。在卡托普利处理的细胞中，苏氨酸激酶B（AKT）磷酸化也增加，随后基础和胰岛素刺激的葡萄糖摄取增强。这些结果表明，卡托普利处理对BC3H-1心肌细胞中胰岛素诱导的早期磷酸化事件有直接影响。
