美国，宾夕法尼亚州，费城（2012年1月9日）–新的研究显示，在人工培养主动脉平滑肌细胞过程中，治疗剂量胰岛素的应用，选择性地刺激了新的弹性纤维的形成。这些结果推进了对糖尿病血管病变分子和细胞学机制的理解。多伦多大学心血管研究室，亚历山大希奈克博士及其同伴发现胰岛素疗法，在Ⅰ型糖尿病患者的动脉粥样硬化性病变的治疗时，诱导新的弹性纤维形成，将机械地稳定斑块的发展，并防止动脉闭塞。

研究显示胰岛素确实刺激人工培养主动脉平滑肌细胞过程中，弹性纤维的沉积在培养的人主动脉平滑肌细胞。数据显示，第一次，低剂量的胰岛素完全通过激活胰岛素受体和触发下游P13K信号通路，诱导弹性效应。胰岛素是通过执行并行机制最终上调弹性纤维的沉积：启动弹性蛋白基因表达和增强弹性蛋白分泌。胰岛素依赖型的弹性蛋白基因的转录，发生在FoxO1转录因子解离之后的具体领域内，由弹性蛋白基因启动因子启动。研究还表明，胰岛素可促进向弹性分泌内涵体的转输，以联系S-GAL/EBP——“伴侣”蛋白以增强分泌。

博士认为结果表明，发现弹性作用的低浓度（0.5 - 10纳米）胰岛素，没有限制于动脉平滑肌细胞。因此，胰岛素也刺激形成的弹性纤维在人类皮肤成纤维细胞和从心脏分离出的肌纤维母细胞。这些观察报告构成了再生医学领域真正的新星1）局部应用小剂量胰岛素，以改善糖尿病患者愈合困难的真皮损伤2）心脏梗塞后为患者全身注射胰岛素，以希望可以减轻胰岛素诱导的弹性纤维沉积形成的适应不良的心肌胶原疤痕。

原文：

Philadelphia, PA, USA (January 9, 2012) – New research reveals that insulin applied in therapeutic doses selectively stimulates the formation of new elastic fibers in cultures of human aortic smooth muscle cells. These results advance the understanding of the molecular and cellular mechanisms of diabetic vascular disease. The study is published in the February issue of the American Journal of Pathology.

"Our results particularly endorse the use of insulin therapy for the treatment of atherosclerotic lesions in patients with type I diabetes, in which the induction of new elastic fibers would mechanically stabilize the developing plaques and prevent arterial occlusions," explained lead investigator Aleksander Hinek, MD, PhD, DSc, Professor, Division of Cardiovascular Research, The Hospital for Sick Children and the Department of Laboratory Medicine and Pathobiology, University of Toronto.

Primary insulin deficiency and decreased cellular sensitivity to insulin have been implicated in the pathogenesis of impaired healing processes, atherosclerosis and hypertension, all frequently observed in patients with both type I and type II diabetes. However, the possibility of a direct contribution of insulin to the cellular and molecular mechanisms that control the production of elastic fibers (elastogenesis) has not been explored. The researchers conducted a series of experiments to determine whether low therapeutic concentrations of insulin would promote the production of elastic fibers in cultures of human aortic smooth muscle cells.

Investigators found that insulin does in fact stimulate the deposition of elastic fibers in cultures of human aortic smooth muscle cells. The data demonstrated, for the first time, that low doses of insulin induce the elastogenic effect solely through the activation of insulin receptor and trigger the downstream activation of the P13K signaling pathway. The ultimate up-regulation of elastic fiber deposition by insulin is executed through two parallel mechanisms: the initiation of elastin gene expression and the enhancement of tropoelastin secretion.

Importantly, the experimental data suggest that insulin-dependent initiation of the elastin gene transcription occurs after dissociation of the FoxO1 transcription factor from the specific domain identified within the elastin gene promoter. The researchers also demonstrated that insulin may facilitate the transportation of tropoelastin into the secretory endosomes, where it can associate with S-GAL/EBP, the "chaperone" protein that enhances secretion.

"We believe that our discovery of the elastogenic action of insulin allows for better understanding of the pathologic mechanisms in which the lack of insulin, in diabetes type I, or insulin resistance, in diabetes type II, contribute to the development of hypertension and the rapid progression of atherosclerosis," concluded Dr. Hinek.

Dr. Hinek further elaborated on the far-reaching effects these data provide: "Importantly, our newest results indicate that the discovered elastogenic effect of low concentrations (0.5-10 nM) of insulin is not restricted to the arterial smooth muscle cells. Thus, insulin also stimulates formation of elastic fibers by human skin fibroblasts and by myofibroblasts isolated from human hearts. These observations constitute a real novelty in the field of regenerative medicine and endorse 1) local application of small doses of insulin for ameliorating difficult healing of dermal wounds in diabetic patients and 2) systemic administration of insulin in patients after heart infarctions, in hope that insulin-induced elastic fiber deposition may alleviate formation of maladaptive collagenous scars in the myocardium."