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      Insulin signaling and the regulation of insect diapause

      review-article
      1 , 2
      Frontiers in Physiology
      Frontiers Media S.A.
      diapause, dauer, insulin signaling, FOXO, Culex pipiens

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          Abstract

          A rich chapter in the history of insect endocrinology has focused on hormonal control of diapause, especially the major roles played by juvenile hormones (JHs), ecdysteroids, and the neuropeptides that govern JH and ecdysteroid synthesis. More recently, experiments with adult diapause in Drosophila melanogaster and the mosquito Culex pipiens, and pupal diapause in the flesh fly Sarcophaga crassipalpis provide strong evidence that insulin signaling is also an important component of the regulatory pathway leading to the diapause phenotype. Insects produce many different insulin-like peptides (ILPs), and not all are involved in the diapause response; ILP-1 appears to be the one most closely linked to diapause in C. pipiens. Many steps in the pathway leading from perception of daylength (the primary environmental cue used to program diapause) to generation of the diapause phenotype remain unknown, but the role for insulin signaling in mosquito diapause appears to be upstream of JH, as evidenced by the fact that application of exogenous JH can rescue the effects of knocking down expression of ILP-1 or the Insulin Receptor. Fat accumulation, enhancement of stress tolerance, and other features of the diapause phenotype are likely linked to the insulin pathway through the action of a key transcription factor, FOXO. This review highlights many parallels for the role of insulin signaling as a regulator in insect diapause and dauer formation in the nematode Caenorhabditis elegans.

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          Most cited references117

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          daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans.

          A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2, a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.
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            Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.

            In many species, reducing nutrient intake without causing malnutrition extends lifespan. Like DR (dietary restriction), modulation of genes in the insulin-signaling pathway, known to alter nutrient sensing, has been shown to extend lifespan in various species. In Drosophila, the target of rapamycin (TOR) and the insulin pathways have emerged as major regulators of growth and size. Hence we examined the role of TOR pathway genes in regulating lifespan by using Drosophila. We show that inhibition of TOR signaling pathway by alteration of the expression of genes in this nutrient-sensing pathway, which is conserved from yeast to human, extends lifespan in a manner that may overlap with known effects of dietary restriction on longevity. In Drosophila, TSC1 and TSC2 (tuberous sclerosis complex genes 1 and 2) act together to inhibit TOR (target of rapamycin), which mediates a signaling pathway that couples amino acid availability to S6 kinase, translation initiation, and growth. We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension. Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction.
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              Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein.

              The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult longevity. We found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not a result of impaired oogenesis in chico females, nor was it consistently correlated with increased stress resistance. The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved.
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                Author and article information

                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                26 May 2013
                22 July 2013
                2013
                : 4
                : 189
                Affiliations
                [1] 1Department of Biology, Baylor University Waco, TX, USA
                [2] 2Departments of Entomology and Evolution, Ecology, and Organismal Biology, Ohio State University Columbus, OH, USA
                Author notes

                Edited by: Xanthe Vafopoulou, York University, Canada

                Reviewed by: Hong Lei, University of Arizona, USA; Michael Strand, University of Georgia, USA

                *Correspondence: Cheolho Sim, Department of Biology, Baylor University, A119, Baylor Science Building, 101 Bagby Avenue, Waco, TX 76798, USA e-mail: cheolho_sim@ 123456baylor.edu;
                David L. Denlinger, Departments of Entomology and Evolution, Ecology, and Organismal Biology, Ohio State University, 300 Aronoff Laboratory, 318 West 12th Avenue, Columbus, OH 43210, USA e-mail: denlinger.1@ 123456osu.edu

                This article was submitted to Frontiers in Invertebrate Physiology, a specialty of Frontiers in Physiology.

                Article
                10.3389/fphys.2013.00189
                3717507
                23885240
                4aa3f2ff-d41f-493f-941d-f77ffd08d165
                Copyright © 2013 Sim and Denlinger.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 26 April 2013
                : 30 June 2013
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 153, Pages: 10, Words: 9378
                Categories
                Physiology
                Review Article

                Anatomy & Physiology
                diapause,dauer,insulin signaling,foxo,culex pipiens
                Anatomy & Physiology
                diapause, dauer, insulin signaling, foxo, culex pipiens

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