Novel strategies and targets for the detection and cure of Diabetes Mellitus

Abstract

In diabetes, adipocyte inflammation leads to altered secretion of adipocytokines. The adipocytokine Nampt was investigated, together with its enzymatic product NMN. Neither Nampt nor NMN showed any influence on cell survival and apoptosis in isolated human islets and did not alter insulin secretion during chronic exposure, but both potentiated insulin secretion if added acutely to high glucose concentrations. Secondly we developed a strategy to monitor the functional à ²-cell mass by measuring Mn2 uptake into à ²-cells by MRI. We were able to show Mn2 signals correlating with functional in vivo tests in STZ and HFD induced diabetes mouse models, pointing to Mn2 MRI as a useful tool to monitor functional à ²-cell mass in vivo. The protein family of the Siglecs was found to be expressed on human islet cells and Siglec-7 showed protective effects on failure and apoptosis of isolated human islets. FACS analyses revealed that mice, in contrast to humans, are not expressing Siglecs in endocrine cells. Due to the lacking expression, Siglec-F knockout did not influence blood glucose levels and in vivo and in vitro insulin secretion of diabetic mice.