Abdulreda M H, Caicedo A, Berggren P-O
Diabetes Research Institute, Diabetes Research Institute Federation Center at the University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
CellR4 Repair Replace Regen Reprogram. 2013;1(2):111-122. Epub 2013 Sep 30.
The World Health Organization projects diabetes prevalence worldwide to be at 4.4% in 2030 compared to 2.8% in the year 2000. These alarming predictions come amid vigorous efforts in diabetes research which have failed so far to deliver effective therapies. Our incomplete understanding of the pathogenesis of diabetes is likely to contribute to the "disconnect" between our research efforts and their translation into successful therapies. Technically, studying the pathophysiology of the pancreatic islets is hindered by the anatomical location of the pancreas, which is deeply embedded in the body, and by lack of experimental tools that enable comprehensive interrogation of the pancreatic islets with sufficient resolution in the context of the natural environment non-invasively and longitudinally. Emerging evidence also indicates that challenges in successful translation of findings in animal models to the human setting are complicated by some inherent structural and functional differences between the mouse and human islets. In this review, we briefly describe the advantages and shortcomings of existing intravital imaging approaches used to study the pancreatic islet biology , and we contrast such techniques with a recently established intravital approach using pancreatic islet transplantation into the anterior chamber of the eye. We also provide a summary of recent structure-function studies in the human pancreas to reveal distinctive features of human islets compared with mouse islets. We finally touch on a recently renewed discussion of the validity of animal models in studying human health and disease, and we highlight the potential utility of "humanized" animal models in studying different aspects of human islet biology and improving our understanding of diabetes.
世界卫生组织预计，到2030年全球糖尿病患病率将达到4.4%，而2000年为2.8%。这些惊人的预测是在糖尿病研究大力开展的背景下出现的，然而迄今为止这些研究未能带来有效的治疗方法。我们对糖尿病发病机制的不完全理解可能是导致我们的研究努力与转化为成功疗法之间出现“脱节”的原因。从技术上讲，研究胰岛的病理生理学受到胰腺解剖位置的阻碍，胰腺深深嵌入体内，还受到缺乏实验工具的影响，这些工具能够在自然环境中以足够的分辨率对胰岛进行非侵入性和纵向的全面研究。新出现的证据还表明，由于小鼠和人类胰岛之间存在一些固有的结构和功能差异，将动物模型中的研究结果成功转化到人类环境中面临的挑战变得更加复杂。在这篇综述中，我们简要描述了用于研究胰岛生物学的现有活体成像方法的优缺点，并将这些技术与最近建立的将胰岛移植到眼前房的活体方法进行了对比。我们还总结了最近在人类胰腺中进行的结构 - 功能研究，以揭示与小鼠胰岛相比人类胰岛的独特特征。我们最后谈到了最近关于动物模型在研究人类健康和疾病方面有效性的重新讨论，并强调了“人源化”动物模型在研究人类胰岛生物学的不同方面以及增进我们对糖尿病理解方面的潜在效用。
