Physiological signaling pathways for adaptive beta cell proliferation and maturation (FWOAL515)

KEY QUESTIONS AND AIMS Principle objective of the current project is the comparison of the beta cell phenotypes in the various physiological conditions of adaptive beta cell proliferation, in comparison with the phenotype of adult, differentiated beta cells. Phenotype is considered here as integration of specialized function (insulin synthesis and secretion measured in vitro) and gene/protein expression pattern (measured in flow-sorted pure cell fractions). We will focus on the major differences of proliferating cells-enriched and basal, non-proliferating beta cells, and on the similarities/differences between different modes of adaptive beta cell proliferation in health and disease. In the proliferation-enriched beta cell populations we will look for specific signaling pathways that are activated/overrepresented, and use these as signature of their upstream signal. This should lead to the identification of novel diagnostic and therapeutic targets in diabetes. The major questions of our project are: 1. How is the increased metabolic need for insulin (e.g. in pregnancy of obesity) measured by the beta cells, and processed to a signal for their adaptive proliferation (or growth)? 2. Can we identify a unique gene expression pattern, common to various states of adaptive beta cell proliferation in health and/or disease?

Keywords:Cell Therapy, Prevention, Transplantation, Diagnostic Tests, Immunology, Cell Death and Survival, Islet Cell Pathology, Islet Cell Biology, Beta Cell Transplantation, Diabetes

Disciplines:Endocrinology