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Stephan Speier
Islet Cell Regeneration
Previous and current research
Type I and type II diabetes are characterized by the inability of beta-cells, the major cell type in pancreatic islets of Langerhans, to secret a sufficient amount of insulin to counteract hyperglycemia. In type I diabetes this is due to a pure loss of beta-cells as result of an autoimmune process, whereas in type II diabetes it is the consequence of a combination of beta-cell loss, beta-cell dysfunction and insulin resistance. Substitution of the failing insulin secreting beta-cell by regeneration is considered a promising alternative for the treatment of diabetes. Therefore, understanding the mechanisms leading to neogenesis and replication of islet cells is of great importance to develop new therapeutic approaches.
Our lab studies the mechanisms leading to regeneration of islet cells in mouse and human. To achieve this, our group puts special emphasis on the use of in situ and in vivo technical platforms to study this complex, interactive process and overcome the limitations of commonly used in vitro methods. In particular we have developed sophisticated methods to visualize and quantify beta cell expansion over time in animal models. We are especially interested under which physiological and pathophysiological conditions neogenesis and/or proliferation contribute to beta-cell mass expansion. Furthermore, we want to investigate the origin of pancreatic endocrine progenitor cells and assess the role of specific regulatory molecules in the signaling pathways, leading to replication of islet cells.
Fig: Noninvasive/ in vivo/ imaging of islets of Langerhans.
The picture shows an islet of Langerhans engrafted on the vascular bed of the iris.
Red: Islet of Langerhans imaged by reflected laser light.
Green: Blood vessels visualized by an injected fluorescent dextran.
(Speier et al, Nat Med 2008, 14(5):574-8)
Future projects and goals
- Assessing the contribution of neogenesis and proliferation to islet-cell regeneration
- Evaluating the role of specific regulatory molecules of beta-cell proliferation
- Development of novel techniques and tools for the study of islet-cell regeneration
- Translation of basic research topics into clinical studies in collaboration with the groups of the Diabetes Research Area of the CRTD
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Selected publications
S. Speier, D. Nyqvist, M. Köhler, A. Caicedo, I. B. Leibiger & P.-O. Berggren (2008). Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eye. Nat Protoc., 3(8):1278-86
O. Cabrera, M. C. Jacques-Silva, S. Speier, S.-N. Yang, M. Köhler, D. M. Berman, N. S. Kenyon, C. Ricordi, A. Caicedo and P.-O. Berggren (2008). Glutamate is a positive autocrine signal for glucagon release. Cell Metab., 7, 545-554. .
S. Speier, D. Nyqvist, O. Cabrera, J. Yu, R. D. Molano, A. Pileggi, T. Moede, M. Köhler, J. Wilbertz, B. Leibiger, C. Ricordi, I. B. Leibiger, A. Caicedo & P.-O. Berggren (2008). Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med., 14(5):574-8.
Speier, S., Gjinovci, A., Charollais, A., Meda, P. & Rupnik, M. (2007). Cx36 - mediated coupling reduces beta-cell heterogeneity, confines the stimulating glucose concentration range and affects insulin release kinetics. Diabetes, 56 1078-86
Speier, S., Yang, S-B., Sroka, K., Rose, T. & Rupnik, M. (2005). KATP-channels in beta-cells in tissue slices are directly modulated by millimolar ATP. Mol Cell Endocrinol., 230 51–58.
Speier, S. & Rupnik, M. (2003). A novel approach to in situ characterisation of pancreatic beta-cells. Pflugers Arch., 446, 553-558.