Diabetes mellitus is a complex and multifactorial disease characterized by progressive loss or dysfunction of the insulin-producing β-cells in the pancreas, leading to chronic hyperglycemia, systemic metabolic complications and, in the long-term, to multi-organ damage and premature death.
Currently, all pharmacotherapies, including insulin supplementation, focus on managing high blood sugar levels and avoiding the secondary complications rather than addressing the underlying cause of diabetes: pancreatic beta cell failure or loss. Research into beta cell protection and regeneration is crucial and holds promises for addressing the root cause of diabetes, offering potential avenues for causal treatment. Glucagon-like peptide 1 (GLP-1) therapy was shown to regenerate beta cells in mice, but this did not translate to human. Early or intensive insulin therapy maintains residual beta cell function, but also causes weight gain and is associated with an increased risk for severe hypoglycaemic episodes. In breakthrough discoveries we identified the insulin inhibitory receptor (inceptor) as a druggable target for beta cell insulin sensitization and protection without the side-effects of insulin. Moreover, we combined GLP-1-mediated safe beta cell delivery of estrogen with a 60% reduced insulin demand to restore beta cell function for diabetes remission.
With our ERC grant “BetaRegeneration”, we aim to decipher cellular and molecular mechanisms of beta cell protection and regeneration. Based on the previous identification and validation of known and novel therapeutic targets, we want to explore new avenues of targeted and combinatorial beta cell protection and regeneration therapies that could stop and revert diabetes progression.
If successful, BetaRegeneration will initiate a paradigm shift from symptomatic to causal diabetes therapy.
