The Islet Pathophysiology Group focuses on defining the mechanisms underlying pancreatic islet malfunction and decreased beta-cell mass in type 2-diabetes. The disease has in recent years been associated to variations in a large number of genes. The big challenge is to understand exactly how these genetic variations affect cellular functions in the pancreatic islets, in order to identify targets for causative treatment.
Focus areas include: 1) The role of the redox environment with particular focus on effectors of NADPH and their consequences for beta-cell function and survival; 2) The role of complement proteins of the innate immune system for control of insulin secretion from the pancreatic beta-cell in health and disease. This is done in collaborate with the group of Anna Blom, Lund University and other international collaborators; and, 3) Ion channels, in particular voltage-gated Ca2+ channels, and their role in type 2-diabetes, in collaboration with some of the leading profiles in the area.
Methods used include the patch-clamp technique in combination with microfluorimetry or cellular imaging techniques such as confocal or TIRF imaging. Imaging methods established include multiphoton imaging and fluorescence spectrum correlation. In addidtion, we perform hormone release assays, immunocytochemistry, standard biochemistry and manipulation of gene expression using RNA interference or viral transfer methods.
In an effort to go beyond the single-gene/one-function paradigm and to develop models that take into account the contribution of several genes and their encoded proteins for the altered cellular functions that predispose for type 2-diabetes, and how aberrations in these networks can be corrected by novel treatments. To do this we analyse gene regulatory co-expression networks in pancreatic islets, followed by functional validation experiments, down to detailed molecular level when appropriate.
An important aspect of protein function is their interactions, addressed by discovery techniques (2-hybrid systems) and focused low-throughput methods (e.g. immunoprecipitation, affinity purification), including those that make it possible to characterize interactions in real-time (fluctuation correlation spectroscopy). After discovery and validation, the ultimate goal is to translate findings into improved diagnostics and novel molecular targets for treatment of type 2-diabetes.
Last updated: January 8, 2014
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