PhD student, Karolinska Institute
Improving our understanding of how the beta cells response to different physiological circumstances
Diabetes mellitus is a disease where individuals are faced with problems with their blood glucose regulation as a result of insufficient or defect insulin secretion. The insulin-secreting beta cells sit in small clusters called the islets of Langerhans deeply embedded in the pancreas, which makes it very difficult to study them. We develop tools to improve our understanding of the beta cell and the islet of Langerhans, and thus tools to help understand what goes wrong with these beta cells as diabetes develops. One way to study beta cells is to use animal models of diabetes. In such animals, we can transplant islets of Langerhans from a donor animal (or human) into the eye of a recipient animal. This can not only cure the diabetes in this recipient animal, it also allows us to look at the transplanted tissue with advanced microscopes. Being able to actually see the beta cells in the living animal before and during the development of diabetes has proven to be very helpful. A second step is to try and intervene in a process that we think goes wrong in the beta cell and may lead to diabetes, and using microscopy see that the beta cells start to work better again.
Abstract: The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease.Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the three-dimensional spatial development and progression of insulitis and beta-cell destruction in pancreata from diabetes-prone NOD and non-diabetes-prone congenic NOD.H-2b mice between 3 and 16 weeks of age.Together with results showing the spatial dynamics of the insulitis process, we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression.Our data provide a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.
Pub.: 16 Apr '10, Pinned: 28 Aug '17
Abstract: The islets of Langerhans constitute the endocrine part of the pancreas and are responsible for maintenance of blood glucose homeostasis. They are deeply embedded in the exocrine pancreas, limiting their accessibility for functional studies. Understanding regulation of function and survival and assessing the clinical outcomes of individual treatment strategies for diabetes requires a monitoring system that continuously reports on the endocrine pancreas. We describe the application of a natural body window that successfully reports on the properties of in situ pancreatic islets. As proof of principle, we transplanted "reporter islets" into the anterior chamber of the eye of leptin-deficient mice. These islets displayed obesity-induced growth and vascularization patterns that were reversed by leptin treatment. Hence, reporter islets serve as optically accessible indicators of islet function in the pancreas, and also reflect the efficacy of specific treatment regimens aimed at regulating islet plasticity in vivo.
Pub.: 20 Nov '13, Pinned: 28 Aug '17
Abstract: Advanced imaging techniques have become a valuable tool in the study of complex biological processes at the cellular level in biomedical research. Here, we introduce a new technical platform for noninvasive in vivo fluorescence imaging of pancreatic islets using the anterior chamber of the eye as a natural body window. Islets transplanted into the mouse eye engrafted on the iris, became vascularized, retained cellular composition, responded to stimulation and reverted diabetes. Laser-scanning microscopy allowed repetitive in vivo imaging of islet vascularization, beta cell function and death at cellular resolution. Our results thus establish the basis for noninvasive in vivo investigations of complex cellular processes, like beta cell stimulus-response coupling, which can be performed longitudinally under both physiological and pathological conditions.
Pub.: 11 Mar '08, Pinned: 28 Aug '17