The aim of our research group is to investigate and to correlate the changes of pancreatic beta cells with other organs in the pathogenesis of type 1 diabetes mellitus (T1DM), an autoimmune disease, and of type 2 diabetes mellitus (T2DM), a metabolic disease. Using morphological, biochemical and molecular morphological methods, the new insights in the pathophysiological mechanism of diabetes development are the basis for rational prevention strategies to inhibit either diabetes development or after diabetes development to inhibit the complete beta cell loss leading to a restoration of the beta cell function by regaining normoglycaemia in an infiltration-free pancreas.
Animal models of human T1DM and T2DM are of particular importance in diabetes research to systematically analyze the pathophysiological mechanisms of beta cell destruction and beta cell regeneration with and without immune cell infiltration in the pancreatic islets. The LEW.1AR1-iddm rat, a spontaneous T1DM model is well characterized. The autoimmune correlate is represented by severely infiltrated islets with activated immune cells releasing pro-inflammatory cytokines leading to the apoptotic beta cell death.
Human pancreatic samples were used to correlate the pathophysiological findings observed especially in this animal model in the context of similarities to the human situation under age-matched non-diabetic and diabetic conditions after T1DM and T2DM manifestation. This is important for a potential transfer of diabetes prevention strategies developed in animal models to humans after disease onset.
The immune cell composition and the cytokine pattern of the infiltrated pancreatic islets are the rational basis for the choice of immune cell and cytokine antibodies as well as small molecules. The therapeutic success is determined by beta cell regeneration, disappearance of the immune cell infiltration of the pancreatic islets, and decrease of pro-inflammatory cytokines in peripheral blood
Our aims are:
- Changes of beta cell cycle and glucose recognition structures in the pancreas of the animal models in comparison to human samples with T1DM and T2DM
- Immune cell changes in lymphatic organs and peripheral blood before and after diabetes development
- Characterization of different forms of T1DM including the LADA form
- Identification of immune cell and cytokine antibodies for the different prevention therapies in the pre-clinical model the LEW.1AR1-iddm rat