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A search for reciprocal signaling between insulin and adipokinetic hormone producing cells in Drosophila
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology. (Nässel)
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Insulin signaling in Drosophila regulates major physiological processes such as stress resistance, growth, carbohydrate and lipid metabolism, aging, reproduction and possibly diapause. Adipokinetic hormone (AKH) signaling originating from the corpora cardiaca (CC) cells, is another crucial regulator of hemolymph carbohydrate levels in Drosophila. These two systems are suggested to have opposing effects on lipid and sugar metabolism in Drosophila, reminiscent of the mammalian insulin and glucagon hormones. We studied the possible functional relationship between the insulin producing cells (IPCs) and the CC cells by interfering with insulin receptor (InR) and AKH receptor (AKH-R) expression on these cells. Our experiments revealed increased carbohydrate and lipid levels after knocking down InR in the CC cells. We also showed that diminished InR levels on the IPCs lead to increased starvation resistance, however we did not observe any changes in carbohydrate or lipid levels. So far we can only suggest action of insulins via its receptor on the IPCs and the CC cells, but we do not have conclusive data for AKH action on IPCs or CC cells.

Keyword [en]
Insulin signaling, insulin receptor, adipokinetic hormone receptor, metabolism, peptide hormones, Drosophila melanogaster
National Category
Cell Biology
Research subject
Functional Zoomorphology
Identifiers
URN: urn:nbn:se:su:diva-80322OAI: oai:DiVA.org:su-80322DiVA: diva2:552971
Funder
Swedish Research Council
Available from: 2012-09-17 Created: 2012-09-17 Last updated: 2012-09-24Bibliographically approved
In thesis
1. Regulation of insulin producing cells, stress responses and metabolism in Drosophila
Open this publication in new window or tab >>Regulation of insulin producing cells, stress responses and metabolism in Drosophila
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Drosophila, neuropeptides have regulatory roles in development, growth, metabolism and reproduction. This study focused on GABA and the neuropeptides Drosophila tachykinin (DTK), short neuropeptide F (sNPF), adipokinetic hormone (AKH), corazonin (CRZ) and Drosophila insulin-like peptides (DILPs) as possible regulators of metabolic stress responses and homeostasis. We showed that metabotropic GABAB receptors (GBRs) are expressed on brain insulin producing cells (IPCs), suggesting an inhibitory regulation of these cells by GABA. Knockdown of GBR on IPCs shortened lifespan and stress resistance, altered carbohydrate and lipid metabolism at stress (paper I). We showed that three different neuropeptides; DTK, sNPF and ITP, are co-expressed in five pairs of adult neurosecretory cells (paper II). ITP-knock down was not studied yet, but sNPF- and DTK-knock down flies showed decreased stress resistance at desiccation and starvation and decreased water levels at desiccation, suggesting that these peptides are involved in water homeostasis during stress conditions. sNPF was previously shown to affect feeding, growth and DILP expression via the IPCs, but it was not known which sNPF-expressing neurons are responsible for these actions. We could identify a specific set of bilateral neurons (DLPs) that co-express sNPF and corazonin that target the IPCs. We showed that these peptides co-released from DLPs regulate DILP transcription and probably release in the adult Drosophila brain and thus have roles in regulation of stress resistance and metabolism (paper III). AKH signaling was previously shown to affect hemolymph carbohydrate levels and lipid stores in Drosophila. Insulin (DILP) signaling and AKH signaling are suggested to have opposing effects on lipid and sugar metabolism in Drosophila. We studied the possible functional relationship between these two systems; do they mutually regulate each other?  Our results suggest action of DILPs via the Insulin Receptor on the IPCs and the AKH producing cells, but we could not provide evidence for AKH action on IPCs or AKH cells (paper IV). 

Place, publisher, year, edition, pages
Stockholm, Sweden: Department of Zoology, Stockholm Univeristy, 2012. 33 p.
Keyword
Insulin signaling, Drosophila melanogaster, peptide hormones, neuropeptides, GABA
National Category
Cell Biology
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-80518 (URN)978-91-7447-582-1 (ISBN)
Public defence
2012-10-26, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Epub ahead of print. Paper 4: Manuscript.

Available from: 2012-10-04 Created: 2012-09-24 Last updated: 2014-10-28Bibliographically approved

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