A NATURAL BODY WINDOW TO STUDY HUMAN PANCREATIC ISLET CELL FUNCTION AND SURVIVAL

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.