Nutritional state-dependent modulation of insulin-producing cells in Drosophila
Insulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta cells and release insulin directly into circulation. To investigate the in vivo dynamics of IPC activity, we quantified the effects of nutritional and in...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/98514 |
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| author | Rituja S Bisen Fathima Mukthar Iqbal Federico Cascino-Milani Till Bockemühl Jan M Ache |
| author_facet | Rituja S Bisen Fathima Mukthar Iqbal Federico Cascino-Milani Till Bockemühl Jan M Ache |
| author_sort | Rituja S Bisen |
| collection | DOAJ |
| description | Insulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta cells and release insulin directly into circulation. To investigate the in vivo dynamics of IPC activity, we quantified the effects of nutritional and internal state changes on IPCs using electrophysiological recordings. We found that the nutritional state strongly modulates IPC activity. IPC activity decreased with increasing periods of starvation. Refeeding flies with glucose or fructose, two nutritive sugars, significantly increased IPC activity, whereas non-nutritive sugars had no effect. In contrast to feeding, glucose perfusion did not affect IPC activity. This was reminiscent of the mammalian incretin effect, where glucose ingestion drives higher insulin release than intravenous application. Contrary to IPCs, Diuretic hormone 44-expressing neurons in the pars intercerebralis (DH44PINs) responded to glucose perfusion. Functional connectivity experiments demonstrated that these DH44PINs do not affect IPC activity, while other DH44Ns inhibit them. Hence, populations of autonomously and systemically sugar-sensing neurons work in parallel to maintain metabolic homeostasis. Accordingly, activating IPCs had a small, satiety-like effect on food-searching behavior and reduced starvation-induced hyperactivity, whereas activating DH44Ns strongly increased hyperactivity. Taken together, we demonstrate that IPCs and DH44Ns are an integral part of a modulatory network that orchestrates glucose homeostasis and adaptive behavior in response to shifts in the metabolic state. |
| format | Article |
| id | doaj-art-4ac9b8255286433983e7af7000fb72b1 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-4ac9b8255286433983e7af7000fb72b12025-01-29T12:22:14ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.98514Nutritional state-dependent modulation of insulin-producing cells in DrosophilaRituja S Bisen0https://orcid.org/0000-0002-8312-7191Fathima Mukthar Iqbal1Federico Cascino-Milani2Till Bockemühl3Jan M Ache4https://orcid.org/0000-0001-7355-7860Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, GermanyNeurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, GermanyNeurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, GermanyDepartment of Animal Physiology, Institute of Zoology, University of Cologne, Cologne, GermanyNeurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, GermanyInsulin plays a key role in metabolic homeostasis. Drosophila insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta cells and release insulin directly into circulation. To investigate the in vivo dynamics of IPC activity, we quantified the effects of nutritional and internal state changes on IPCs using electrophysiological recordings. We found that the nutritional state strongly modulates IPC activity. IPC activity decreased with increasing periods of starvation. Refeeding flies with glucose or fructose, two nutritive sugars, significantly increased IPC activity, whereas non-nutritive sugars had no effect. In contrast to feeding, glucose perfusion did not affect IPC activity. This was reminiscent of the mammalian incretin effect, where glucose ingestion drives higher insulin release than intravenous application. Contrary to IPCs, Diuretic hormone 44-expressing neurons in the pars intercerebralis (DH44PINs) responded to glucose perfusion. Functional connectivity experiments demonstrated that these DH44PINs do not affect IPC activity, while other DH44Ns inhibit them. Hence, populations of autonomously and systemically sugar-sensing neurons work in parallel to maintain metabolic homeostasis. Accordingly, activating IPCs had a small, satiety-like effect on food-searching behavior and reduced starvation-induced hyperactivity, whereas activating DH44Ns strongly increased hyperactivity. Taken together, we demonstrate that IPCs and DH44Ns are an integral part of a modulatory network that orchestrates glucose homeostasis and adaptive behavior in response to shifts in the metabolic state.https://elifesciences.org/articles/98514Insulinincretin effectmetabolic homeostasisin vivo electrophysiologyneuronal circuitslocomotion |
| spellingShingle | Rituja S Bisen Fathima Mukthar Iqbal Federico Cascino-Milani Till Bockemühl Jan M Ache Nutritional state-dependent modulation of insulin-producing cells in Drosophila eLife Insulin incretin effect metabolic homeostasis in vivo electrophysiology neuronal circuits locomotion |
| title | Nutritional state-dependent modulation of insulin-producing cells in Drosophila |
| title_full | Nutritional state-dependent modulation of insulin-producing cells in Drosophila |
| title_fullStr | Nutritional state-dependent modulation of insulin-producing cells in Drosophila |
| title_full_unstemmed | Nutritional state-dependent modulation of insulin-producing cells in Drosophila |
| title_short | Nutritional state-dependent modulation of insulin-producing cells in Drosophila |
| title_sort | nutritional state dependent modulation of insulin producing cells in drosophila |
| topic | Insulin incretin effect metabolic homeostasis in vivo electrophysiology neuronal circuits locomotion |
| url | https://elifesciences.org/articles/98514 |
| work_keys_str_mv | AT ritujasbisen nutritionalstatedependentmodulationofinsulinproducingcellsindrosophila AT fathimamukthariqbal nutritionalstatedependentmodulationofinsulinproducingcellsindrosophila AT federicocascinomilani nutritionalstatedependentmodulationofinsulinproducingcellsindrosophila AT tillbockemuhl nutritionalstatedependentmodulationofinsulinproducingcellsindrosophila AT janmache nutritionalstatedependentmodulationofinsulinproducingcellsindrosophila |