Pancreatic β- and α-cell adaptation in response to metabolic changes

Insulin-producing pancreatic _-cells are essential to maintain blood glucose levels within a narrow range. _-cells can adapt to an increased insulin demand by enhancing insulin secretion via increased _-cell function and/or increased _-cell mass. Inadequate _-cell adaptation leads to hyperglycemia and eventually diabetes mellitus. Therefore, it is critical to understand how the _-cell mass is regulated. We investigated _- and _-cell adaptation in response to different metabolic changes. We found that _-cell adaptation in response to insulin resistance in mice, rats, and deceased organ donors was regionally heterogeneous throughout the pancreas. We also observed that the glucagon-producing _-cell mass adapts to metabolic changes, resulting in the maintenance of the _- to _-cell ratio. Furthermore, we show that treatment of normoglycemic mice with a glucagon-like-peptide-1 receptor agonist improved _-cell function and that this is associated with a decrease in _-cell mass in order to maintain normoglycemia. In mice fed a high-fat, low-carbohydrate ketogenic diet beta-cell adaptation failed, resulting in symptoms that are associated with diabetes in humans. Finally, we developed three high-throughput culture platforms for human islets to assess _-cell function that can be used in future studies to identify novel mechanisms involved in _- and _-cell adaptation.The research presented in this thesis was supported by the Diabetes Cell Therapy Initiative consortium, the Dutch Diabetes Research Foundation, the DON foundation, the Bontius Foundation and an unrestricted research grant from Novo Nordisk.UBL - phd migration 201

Informe final del proyecto "Vídeos per a l'aprenentatge inclusiu" (2014PID-UB/016)

El proyecto “Vídeos para el aprendizaje inclusivo: diseño de un flujo de trabajo para la creación, descripción, publicación y difusión de recursos de aprendizaje accesible en formato vídeo”, llevado a término bajo la dirección de Miquel Centelles y varios miembros del grupo Adaptabit con la colaboración de Iván Pérez y Andreu Sulé, ha estudiado la descripción enriquecida de los videos docentes atendiendo a sus características pedagógicas y de accesibilidad digital. Para ello ha propuesto una extensión del esquema de metadatos básico usado en el Depósito Digital de la Universidad de Barcelona según las pautas Learning Resources Metadata Initiative y Access for all 3.0. Tras adaptar las condiciones de accesibilidad de 4 vídeos existentes en el depósito digital, ha implementado el esquema de metadatos enriquecido en una copia local del repositorio DSpace de la Universidad de Barcelona y ha implementado también una conversión automática de estos metadatos a microdatos schema.org para una mayor visibilidad en buscadores generalistas. Como resultado se cuenta con una prueba piloto de unos recursos accesibles, descritos adecuadamente y visibles también para los buscadores como Google, Yahoo o Bing.Programa de Millora i Innovació Docent de la Universidad de Barcelona, 2014PID-UB/01

Plasma levels of von Willebrand factor, von Willebrand factor propeptide and factor VIII in carriers and patients with nephrogenic diabetes insipidus.

Thrombosis and Hemostasi

Pancreatic alpha-cell mass in obesity

Nephrolog

Glucagon-like peptide-1 receptor agonist treatment reduces beta cell mass in normoglycaemic mice

Nephrolog

Beta cell adaptation is topologically heterogeneous throughout the pancreas

Nephrolog

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice

AIMS: Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. METHODS: C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. RESULTS: SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. CONCLUSIONS: HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment

Loss of beta-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits

Nephrolog