The etiology of metabolic syndrome and type 2 diabetes is complex and involves the interaction between both genetic and environmental factors including nutritional state with consequent metabolic signals. There are currently no clinical treatments to prevent, reverse, or efficiently cure the progression of rapid beta-cell demise or insulin resistance in diabetes-prone individuals which means that there is a need for novel therapies for these conditions. We have recently shown that it is possible to restore the normal function of beta-cells by blocking the protein VDAC1 (Voltage-Dependent Anion Channel 1), which is dramatically increased in beta cells of people with T2D. Targeting VDAC1 may lead to the prevention of T2D progression in diabetes-prone subjects.

Increased VDAC1 has also been reported in the affected nerves in Alzheimer's disease. We therefore believe that investigating the mechanism behind increased VDAC1 expression and its mistargeting to the cell surface in beta cells in pathophysiological conditions can also be of great importance for other human diseases.

Aims

• Studying the mechanisms underlying increased VDAC1 expression and membrane translocation in pancreatic beta cells, vascular endothelial cells, adipocytes, and macrophages in pathological conditions such as long-lasting hyperglycemia or low-grade inflammation.
• To investigate VDAC1 expression in peripheral insulin target tissues such as adipocytes, endothelial, and macrophages under hyperglycemia and inflammatory conditions.
• To develop and test new VDAC1 inhibitors as anti-diabetic drugs in cell-based in vitro models as well as in animal models of diabetes. 

Impact

Our research projects will contribute to new insights into the mechanism behind cell dysfunction and demise as well as the mechanism behind the development of insulin resistance in peripheral insulin-targeted tissues. The long-term goal is to develop a new class of drugs, which targets the mitochondrial protein VDAC1. This protein has been mistargeted to the cell membrane, causing ATP loss that results in cell dysfunctionality.

Research output

Link to a list of research output by the group in Lund University's research portal

Team members

Link to a list of team members in Lund University's research portal