Insulin and Immunity: when complement takes control
We are studying an unexpected role of complement – in the physiology and metabolism of pancreatic beta-cells. Surprisingly, this is related to intracellular functions of complement and therefore changes the way we perceive this “blood” system and will likely inspire discovery of many other intracellular effects of complement.
We study the role of intracellular complement factor C3 and membrane bound complement inhibitor CD59 in insulin secretion as well as physiology and metabolism of beta cells.
We have shown recently that C3 regulates autophagy due to its ability to interact with ATG16L1 and now we want to delineate how C3 enters cytoplasm and what are molecular mechanisms by which it is regulating autophagy. We identified two novel cytoplasmin siforms of CD59, which are required for insulin secretion and we are now studying the mechanism underlying this phenomenon as well as physiological importance using mouse models.
This interdisciplinary project utilizes very advanced methods such as cutting edge imaging, bioinformatics, electrochemistry, in vivo rodent models and clinical datasets.
The long-term goal of these projects I to relate all the above findings to type 2 diabetes in hope of developing new therapeutic avenues.
C3 project is funded by Knut and Alice Wallenberg Foundation
https://kaw.wallenberg.org/en/research/known-protein-unknown-role-diabetes-and-infection
CD59 project is funded by
Funding is also provided by Diabetesfonden
Anna Blom and Erik Renström
