Størling Group – Islet Pathophysiology
Our research focuses on inflammation- and immune-mediated pancreatic islet dysfunction and destruction in type 1 diabetes. Our aim is to decipher the detrimental events induced by immune factors in islets to obtain detailed mechanistic insight into beta-cell destruction and alpha-cell failure in type 1 diabetes.
Our research aims at uncovering changes in gene networks and elucidating how specific disease risk genes affect islet function and vulnerability to immune destruction. My shared position between Department of Biomedical Sciences and Steno Diabetes Center Copenhagen (SDCC) allows for close cooperation with clinical researchers to maximize the translational aspect of our work. It is our hope that our research can be exploited to develop new medicines to prevent beta-cell destruction and alpha-cell dysfunction in type 1 diabetes.
Beta-cell destruction in type 1 diabetes
Type 1 diabetes is caused by a complex interplay between genetic and environmental factors that result in an autoimmune attack against the beta cells. To obtain detailed insight at the molecular level into beta-cell failure in T1D, we are investigating various aspects of cytokine-induced beta-cell destruction, including:
- The role of beta-cell-expressed T1D risk genes in regulating the beta cells’ fragility and sensitivity to inflammatory stress and death.
- The intrinsic death mechanisms induced by cytokines in beta cells.
Alpha-cell dysfunction in type 1 diabetes
For reasons that are currently unclear, the glucagon-secreting alpha cells become dysfunctional in T1D. Specifically, the counterregulatory glucagon response to low blood glucose to avoid hypoglycemia is attenuated and there is a paradoxical glucagon release in response to meal ingestion. This relatively new research in our group focuses on understanding the mechanisms underlying alpha-cell dysfunction in T1D to develop novel therapeutic options to revive the alpha-cells’ response to dips in blood glucose. Our research in this area include:
- Investigations of the role of gut hormones in regulating glucagon secretion.
- Studying how diabetogenic cytokines affect alpha-cell function.
- Deciphering the genes and signalling pathways responsible for alpha-cell dysfunction in T1D.
- Model systems include human islets, islet spheroids, EndoC-βH5 cells, induced pluripotent stem cells.
- Evaluation of cell death, apoptosis, toxicity, and viability.
- Transfection techniques.
- Gene knockdown techniques.
- Cellular signal transduction.
- Transcriptomics and gene networks
- Glucose-stimulated insulin and glucagon secretion.
- Inflammatory biomarkers by multiplex analyses.