Modulation of Insulin-Producing Cells in Drosophila
1 Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Am Hubland, 97074 Würzburg, Germany
Insulin plays a key role in regulating metabolic homeostasis and other important bodily functions in vertebrates and invertebrates. In Drosophila, insulin is predominantly released by Insulin-Producing Cells (IPCs) in the central brain and acts as a neuromodulator within the nervous system and on tissues throughout the body. Therefore, IPC activity and insulin release must be dynamically adjusted to internal demands. Here, we investigate fundamental principles of IPC modulation in Drosophila, by combining in vivo physiology with neurogenetics and detailed anatomical analyses. We tackle two core questions about IPC modulation: first, we examine how the nutritional state and internal state changes shape IPC activity. Second, we quantify how other modulatory systems affect the IPC activity. Our results demonstrate that the IPC activity is highly dependent on the feeding state. Furthermore, glucose ingestion but not glucose perfusion significantly increases the IPC activity which is reminiscent of the mammalian incretin effect. By investigating the physiological effects of key aminergic and peptidergic inputs on the IPC activity, we reveal a strong modulation on fast time scales. Some of these inputs shift the overall IPC population activity towards an excited state, while others shift the IPC activity towards inhibition. In addition, we demonstrate that the IPC population has a heterogeneous receptor profile. Interestingly, this heterogeneity is also evident in physiological responses to modulatory inputs, such that certain inputs excite one subset of the IPCs, while inhibiting another. Taken together, we compile an extensive, multi-level framework for the modulation of the insulinergic system in Drosophila, which reveals a high level of regulatory flexibility.