Insulin induces a hypercontractile airway smooth muscle phenotype

Insulin induces a hypercontractile airway smooth muscle phenotype
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DOI:
10.1016/j.ejphar.2003.08.081
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发表时间:
2003-11-14
影响因子:
5
通讯作者:
Zaagsma, J
Zaagsma, J
中科院分区:
医学2区
文献类型:
--
作者:
Gosens, R;Nelemans, SA;Zaagsma, J

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本研究旨在探讨胰岛素对体外培养的牛气管平滑肌表型的影响。肌条的收缩性和分离细胞的dna合成([3 H]胸苷结合)作为平滑肌表型的参数。胰岛素(1mum)对牛气管平滑肌有丝分裂作用,并能增强其他生长因子诱导的dna合成。相比之下,未传代的牛气管平滑肌细胞经预处理后,生长因子诱导的有丝分裂反应明显减弱,但在基础掺入方面没有差异。用胰岛素预处理器官培养的牛气管平滑肌条增加了对甲胆碱和KCl的最大收缩。这些结果表明,在其他生长因子存在的情况下,胰岛素会急剧增加dna合成。相反,胰岛素预处理诱导有丝分裂能力下降的过度收缩表型。这一机制可能与哮喘和I型糖尿病之间的负相关有关。此外,这些发现可能对雾化胰岛素在糖尿病中的应用有启示。(C) 2003 Elsevier B.V.版权所有
This study aims to investigate the effects of insulin on bovine tracheal smooth muscle phenotype in vitro. Contractility of muscle strips and DNA-synthesis ([3 H]thymidine incorporation) of isolated cells were used as parameters for smooth muscle phenotyping. Insulin (1 muM) was mitogenic for bovine tracheal smooth muscle and potentiated DNA-synthesis induced by other growth factors. In contrast, after pretreatment of unpassaged bovine tracheal smooth muscle cells in culture, the mitogenic response induced by growth factors was strongly diminished, with no difference in the basal incorporation. Pretreatment of bovine tracheal smooth muscle strips in organ culture with insulin increased maximal contraction to methacholine and KCl. These results show that insulin acutely augments DNA-synthesis in the presence of other growth factors. In contrast, insulin pretreatment induces a hypercontractile phenotype with a decreased mitogenic capacity. This mechanism may be involved in the putative negative association between asthma and type I diabetes. In addition, these findings may have implications for the use of aerosolized insulin in diabetes mellitus. (C) 2003 Elsevier B.V. All rights reserved.