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Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
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2011 (English)In: Journal of Experimental Biology, ISSN 0022-0949, E-ISSN 1477-9145, Vol. 214, 4201-4208 p.Article in journal (Refereed) Published
Abstract [en]

Drosophila insulin-like peptides (DILPs) play important hormonal roles in the regulation of metabolic carbohydrates and lipids, but also in reproduction, growth, stress resistance and aging. In spite of intense studies of insulin signaling in Drosophilag the regulation of DILP production and release in adult fruit flies is poorly understood. Here we investigated the role of Drosophila tachykinin-related peptides (DTKs) and their receptors, DTKR and NKD, in the regulation of brain insulin-producing cells (IPCs) and aspects of DILP signaling. First, we show DTK-immunoreactive axon terminations close to the presumed dendrites of the IPCs, and DTKR immunolabeling in these cells. Second, we utilized targeted RNA interference to knock down expression of the DTK receptor, DTKR, in IPCs and monitored the effects on Dilp transcript levels in the brains of fed and starved flies. Dilp2 and Dilp3, but not Dilp5, transcripts were significantly affected by DTKR knockdown in IPCs, both in fed and starved flies. Both Dilp2 and Dilp3 transcripts increased in fed flies with DTKR diminished in IPCs whereas at starvation the Dilp3 transcript plummeted and Dilp2 increased. We also measured trehalose and lipid levels as well as survival in transgene flies at starvation. Knockdown of DTKR in IPCs leads to increased lifespan and a faster decrease of trehalose at starvation but has no significant effect on lipid levels. Finally, we targeted the IPCs with RNAi or ectopic expression of the other DTK receptor, NKD, but found no effect on survival at starvation. Our results suggest that DTK signaling, via DTKR, regulates the brain IPCs.

Place, publisher, year, edition, pages
2011. Vol. 214, 4201-4208 p.
National Category
Zoology
Research subject
Functional Zoomorphology
Identifiers
URN: urn:nbn:se:su:diva-65951DOI: 10.1242/jeb.062091ISI: 000297684200020PubMedID: 22116763OAI: oai:DiVA.org:su-65951DiVA: diva2:466557
Available from: 2011-12-16 Created: 2011-12-16 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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