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Insulin Production and Signaling in Renal Tubules of Drosophila is under Control of Tachykinin-related Peptide and Regulates Stress Resistance
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
The Burnham Institute for Medical Research.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.ORCID iD: 0000-0002-1147-7766
2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, e19866- p.Article in journal (Refereed) Published
Abstract [en]

The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolichomeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of whichare produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renaltubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but alsoplay roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules byDrosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells.Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted inincreased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus,stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations ofS6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locallyon tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in therenal tubules and that this signaling is under control of stress-induced release of peptide hormone.

Place, publisher, year, edition, pages
2011. Vol. 6, no 5, e19866- p.
Keyword [en]
Insulin signaling, peptide signaling, insulin, stress
National Category
Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
URN: urn:nbn:se:su:diva-62505DOI: 10.1371/journal.pone.0019866ISI: 000290440200031OAI: oai:DiVA.org:su-62505DiVA: diva2:442442
Funder
Swedish Research Council, 621-2007-6500
Available from: 2011-09-21 Created: 2011-09-21 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Neuropeptides and GABA in control of insulin producing cells in Drosophila
Open this publication in new window or tab >>Neuropeptides and GABA in control of insulin producing cells in Drosophila
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Insulin plays an important role in metabolic regulation as well as in growth, fecundity and stress resistance. In order to understand more about the regulation of insulin-like peptide (DILP) production and release we investigate the impact of neuropeptide (DTK) signaling and classical neurotransmitter (GABA) signaling onto the insulin producing cells of the Drosophila brain.

DTK was shown to regulate insulin production through DTK receptors found on the insulin producing cells of the brain. DTK has an impact on carbohydrate and lipid levels as well as effect stress resistance (Paper I). Manipulations of DTK signaling differentially affect Dilp transcript levels. We also showed that GABA regulates the production and release of insulin-like peptides via GABABRs (Paper II). Both these two signaling pathways have an inhibitory action on insulin production and release.

The Malpighian (renal) tubules were discovered as a novel site of insulin-like peptide expression and DTK signaling was shown to converge on the insulin pathway also here (Paper III). Stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP 5 signaling. Manipulations of superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP 5 acts locally on tubules, possibly in oxidative stress regulation.

Finally, we demonstrated that a cholecystokinin-like (CCK) peptide, DSK, is present in the IPCs and affects meal size regulation and food preference (Paper IV). DSK, like CCK, therefore acts to induce satiety. DSK and Dilp transcripts levels were also found to affect each other, suggesting coordination and possibly a feedback mechanism between the two signaling pathways.

In summary, we have studied control of Insulin signaling in Drosophila and have found that the different DILP isoforms have may separate functions and that they are separately regulated by both neuropeptides and classical neurotransmitters.

Place, publisher, year, edition, pages
Stockholm: Department of Zoology, Stockholm University, 2011. 40 p.
Keyword
Drosophila, insulin signaling, metabolism, feeding, DTK, DSK, GABA, stress resistance
National Category
Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-62542 (URN)978-91-7447-374-2 (ISBN)
Public defence
2011-10-28, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 621-2007-6500
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 4: Manuscript. Available from: 2011-10-06 Created: 2011-09-22 Last updated: 2012-01-12Bibliographically approved

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