STIMULATORY EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I ON MIGRATION AND TUBE FORMATION BY VASCULAR ENDOTHELIAL-CELLS
STIMULATORY EFFECTS OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I ON MIGRATION AND TUBE FORMATION BY VASCULAR ENDOTHELIAL-CELLS
复制标题
DOI：
10.1016/0021-9150(92)90273-j
复制
发表时间：
1992-02-01
期刊：
影响因子：
5.3
通讯作者：
MUROTA, S
中科院分区：
文献类型：
--
作者：
NAKAOHAYASHI, J;ITO, H;MUROTA, S
以牛颈动脉内皮细胞为研究对象，研究胰岛素和胰岛素样生长因子I（IGF-I）对内皮细胞迁移、增殖和成管活性的影响。通过滤膜技术测定迁移，并通过我们最近开发的定量血管生成体外模型测定管形成。在该模型中，内皮细胞在两层 I 型胶原凝胶之间培养，并组织成管状结构，模拟体内超微结构的毛细血管。胰岛素 (50-1000-mu-units/ml) 和 IGF-I (10-200 ng/ml) 以剂量依赖性方式显着刺激内皮细胞的迁移，其中胰岛素在 1000-mu-units/ml 时最大刺激为 3.0 倍，对于 IGF-I 在 200 ng/ml 时最大刺激为 3.8 倍 (P < 0.01)。浓度高达 1000 微单位/毫升的胰岛素和浓度高达 100 纳克/毫升的 IGF-I 不会影响内皮细胞的增殖。当在胶原凝胶的培养基中添加胰岛素或IGF-I时，内皮细胞的管形成活性被显着刺激。随着胰岛素浓度从25μunits/ml增加到100μunits/ml，管的具体长度显着增加（P<0.01）。在 100-mu-units/ml 时，刺激是 1.77 倍（P < 0.01）。 IGF-I (1-100 ng/ml) 还可以剂量依赖性地刺激管的伸长，在 100 ng/ml 时最大刺激为 1.96 倍（P < 0.01）。因此，病理生理浓度的胰岛素和IGF-I刺激内皮细胞的迁移和管形成活性，表明这些多肽可以在动脉粥样硬化等情况下刺激内皮损伤的修复，并且可以充当血管生成的刺激剂。
The effects of insulin and insulin-like growth factor I (IGF-I) on migration, proliferation and tube-forming activity of endothelial cells were investigated, by using bovine carotid artery endothelial cells. Migration was assayed by a filter membrane technique and tube formation was assayed by a quantitative angiogenesis in vitro model which we have recently developed. In this model, endothelial cells are cultured between two layers of type I collagen gel and become organized into tube-like structures which mimic capillaries in vivo ultrastructurally. Insulin (50-1000-mu-units/ml) and IGF-I (10-200 ng/ml) significantly stimulated migration of endothelial cells in a dose-dependent manner with a maximal stimulation of 3.0-fold at 1000-mu-units/ml for insulin and 3.8-fold at 200 ng/ml for IGF-I (P < 0.01). Insulin at concentrations up to 1000-mu-units/ml and IGF-I up to 100 ng/ml did not affect proliferation of endothelial cells. When insulin or IGF-I was added in culture medium on collagen gels, tube-forming activity of endothelial cells was markedly stimulated. The specific lengths of tubes significantly increased with the increase in insulin concentration from 25 to 100-mu-units/ml (P < 0.01). At 100-mu-units/ml, the stimulation was 1.77-fold (P < 0.01). IGF-I (1-100 ng/ml) also stimulated the elongation of tubes dose-dependently with a maximal stimulation of 1.96-fold at 100 ng/ml (P < 0.01). Thus, insulin and IGF-I at pathophysiological concentrations stimulate migration and tube-forming activity of endothelial cells, suggesting that these polypeptides may stimulate repair of endothelial injury in cases such as atherosclerosis and may act as a stimulator of angiogenesis.