No description available.

No description available.

The purpose of this study is to describe and compare the D cells of the islets of Langerhans in six different species of mammals.

Thesis (M.D.)—Boston University

Thesis (doctoral)--University of Uppsala, 1982. / Includes bibliographical references (p. 23-24).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Islet transplantation for the purpose of treating insulin-dependent diabetes is currently limited by several factors, most significantly, islet survival post transplantation. In the following dissertation, a tissue-engineered prevascularized pancreatic encapsulating device (PPED) was designed, developed, and evaluated. Microvessel fragments placed within a 3-dimensional collagen-based matrix produce and secrete vascular endothelial growth factor, and inosculate with the host circulation. Isolated islets placed within collagen gels exhibited four-fold more insulin release in response to glucose stimulation than islets in tissue culture. The insulin released by β-cells in islets encapsulated in collagen exhibited unobstructed diffusion within the collagen gels. Subsequent studies evaluated the ability to create a sandwich comprised of two layers of prevascularized collagen gels around a central collagen gel containing islets. In vitro characterization of the islets within these constructs showed that islets are functional and respond to glucose stimulation. The PPEDs were implanted subcutaneously into SCID mice. Islet survival was assessed after 7, 14, and 28 days. Immunohistochemical analysis was performed on the implants to detect insulin and the presence of intraislet endothelial cells. At all time points, insulin was localized in association with intact and partially dissociated islets. Moreover, cells that exhibited insulin staining were co-localized with intraislet endothelial cells. Lastly, dextran-perfused PPEDs showed host perfusion throughout the implant, including perfusion to structures that are morphologically consistent with pancreatic islets. These data indicate that the PPED enhances islet survival by supporting islet viability, by maintaining intraislet endothelial cells, and by enhancing reperfusion to the islets.

Pro-inflammatory cytokines released from immune cells infiltrating the endocrine pancreas in Type 1 Diabetes (T1D) induce the generation of reactive oxygen and nitrogen species (ROS/RNS). Cytokines are in part cytotoxic to ƓÒ-cells via the production of peroxynitrite (ONOO-). ƓÒ-cell are weakly protected against the toxicity of ROS/RNS because of limited expression of antioxidant enzymes. The purpose of this study was to evaluate the expression and regulation of Peroxiredoxins (Prdxs/PRDXs), a new family of antioxidant enzymes in islet ƓÒ-cell. Peroxiredoxin 5 (Prdx5) is ubiquitously expressed in mammals and it exhibits a range of cellular roles including cytoprotective antioxidant defence. Human PRDX5 possesses a peroxynitrite reductase activity but its role in ƓÒ-cell defence was not investigated yet. In a first set of experiments, the localization of the Prdx family was analyzed in rodent pancreas. Prdx1 was preferentially found in the non-b-cells of the islet and in exocrine tissue. Prdx2, Prdx3 and Prdx5 were present in b and non-b-cells, while Prdx4 and Prdx6 were poorly expressed. Then, we investigated the modulation of Prdx mRNA and protein expression levels by cytokines in adult rat isolated islets. Prdx1, Prdx2 and Prdx3 expression was not modified while Prdx5 mRNA was upregulated. However, Prdx5 protein was downregulated, which could involve ubiquitination and proteasomal degradation. Little is known about the PRDX antioxidant enzyme expression in human islets. In a second set of experiments, we investigated the expression and regulation of the 6 PRDXs in human islet preparations facing the context of T1D pathogenesis. PRDX 2, 3, 5, 6 were observed in the exocrine part of the pancreas. PRDX2 and PRDX6 were preferentially expressed in islet ƓÑ cells rather than in ƓÒ cells. PRDX3 and PRDX5 were localized in ƓÑ cells as well as in ƓÒ cells. PRDX4 was detected neither in exocrine nor in endocrine tissue. Islets exposed to a mixture of cytokines showed a downregulation of PRDX2, 3, 5, 6 mRNA expression, as was also the case for PRDX5 protein. This study demonstrated that a clear difference between human and rodent species does exist in terms of tissue localization, expression and regulation of Prdxs by cytokines. Finally, we performed Prdx5 overexpression or silencing in insulin secreting cell line INS-1E. Overexpression of Prdx5 was effective against a stress induced by SIN-1 but not against the cytokines mixture. On the opposite, silencing Prdx5 expression decreased the cell viability. Then, the hypothesis that the vulnerability of islets to cytokines mixture was due to the Prdx5 downregulation was not demonstrated. However, the modification of Prdx5 expression would in part be responsible for the high sensitivity of ƓÒ-cell to peroxynitrite. In conclusion, this study featured the presence of some Prdxs/PRDXs in islet cells, and the regulation of their expression by cytokines. They intervene in protection against ONOO- toxicity but their implication against cytokine agression remain to be more precisely evaluated.