Prof. Dr. Marc Donath
Klinik für Endokrinologie, Diabetologie und Klinische Ernährung
CH-4031 Basel, Schweiz
Islet inflammation in type 2 diabetes
Our research focuses on the mechanisms and therapy of decreased insulin production by the pancreatic islets in the obesity associated type 2 diabetes. In previous studies we demonstrated that the metabolic stress evoked by high glucose and saturated fatty acids (contained in animal fat) may induce death of the insulin producing beta-cells of the islets. Subsequently we identified interleukin 1 beta as a key mediator of these deleterious effects and showed that it is produce by human beta-cells in type 2 diabetes. More recently we published several additional studies supporting the concept that this mechanism leads to an inflammatory process and underlies the failure to produce sufficient amount of insulin in type 2 diabetes. On the basis of this we initiated clinical trials with IL-1β antagonists in patients with type 2 diabetes that vindicates this hypothesis and opens the way for a causative treatment. The overall goal of the present projects aim at understanding the precise role and regulation of the uncovered islet inflammation in type 2 diabetes and test therapeutic intervention.
Relation to Clinics
Based on preclinical studies, we hypothesize that components of islet inflammation are initially an attempt of the islet to adapt and repair itself in response to stressors inducing beta cell death. If this initially physiological response is sustained over a prolonged period of time at a high level of activity it becomes deleterious. Therefore, remodeling this response may promote beta-cell survival and regeneration. Understanding the putative beneficial role of these islet-derived cytokines and chemokines in islet regeneration is the scientific problem that is addressed. It opens the door to therapeutic strategies aiming at remodeling this response both in type 1 and 2 diabetes. Several drugs which modulate the action of cytokines and chemokines are presently in clinical trials in our clinical research team.