Junior Research Group

"Primary Cilia and Energy Metabolism"

Goal: To elucidate the role of ciliary signal transduction in energy metabolism

To date, Type 2 Diabetes mellitus poses a major global health threat, affecting more than 31 million people in the European Union alone. In spite of the availability of insulin/ islet hormone replacement therapies and other orally available medication, Type 2 Diabetes is the fifth leading cause of death worldwide. Our research is focused of the role of ciliary signal transduction in Type 2 Diabetes disease risk, general energy metabolism and glucose metabolism in particular. We have evidence that cilia function integrates several aspects of energy metabolism including cellular bioenergetics, insulin sensitivity and secretion.

We recently showed that primary cilia on insulin secreting beta-cells are implicated in Type 2 Diabetes susceptibility. Currently, we are further characterizing the role of primary cilia in central and peripheral insulin action and studying the link between mitochondrial and ciliary function. Current research projects include:

The role of primary cilia in islet hormone regulation

The pancreatic islet secretes a number of peptide hormones that regulate each other’s function; these have to be tightly regulated to maintain glucose homeostasis. Insulin action is balanced by glucagon which stimulates an increase in blood glucose levels; glucagon is secreted by α-cells in response to low glucose levels. Pancreatic somatostatin is produced by δ-cells, acting as a paracrine inhibitor of other pancreatic hormones, namely glucagon and insulin. α-, β- and δ-cells are ciliated and we are investigating the role of primary cilia in the regulation of endocrine islet hormones.

Ciliary function and peripheral insulin action

In European populations, T2DM is typically characterized by a combination of insulin resistance in the “periphery” (skeletal muscle, liver, fat) and defective insulin secretion in the “center”- the pancreatic islet. Skeletal muscle is the main site of post-prandial glucose uptake, roughly 80% of the total load. In addition, skeletal muscle is also ciliated. We are testing the hypothesis, that ciliary dysfunction both in pancreatic islets and skeletal muscle contributes to T2DM and metabolic syndrome.

Interplay of ciliary and mitochondrial function

Biological aging is a complex process, and one of the major mechanisms presently discussed is a decline of mitochondrial energy production or mitochondrial biogenesis over time. One of the hallmarks of T2DM is the late onset; the factors leading to disease manifestation, however, are only insufficiently understood. We are currently investigating a potential link between mitochondrial and ciliary function.

Method development

We are developing assays for the functional characterization of primary cilia. Ciliary function can be characterized by several parameters including ciliary signal transduction or intra-flagellar trafficking of particles along the ciliary axoneme. Our approach relies on (live-)imaging techniques based on fluorescent microscopy methods including super-resolution microscopy.

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