An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control

Brogiolo, Walter; Stocker, Hugo; Ikeya, Tomoatsu; Rintelen, Felix; Fernández, Rafael; Hafen, Ernst

doi:10.1016/s0960-9822(01)00068-9

Cited by 1,133 publications

(1,215 citation statements)

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“…This protein was first identified in B. mori and has been found ubiquitously in Lepidoptera (Nagasawa et al, 1986 (Brogiolo et al, 2001). Dilps 1-5 are more conserved relative to vertebrate insulin-like proteins than Dilp-6 and Dilp-7, but all are structurally similar to the insulin-like superfamily of proteins.…”

Section: Insulin-like Proteins In Insectsmentioning

confidence: 99%

“…Dilps 1-5 are more conserved relative to vertebrate insulin-like proteins than Dilp-6 and Dilp-7, but all are structurally similar to the insulin-like superfamily of proteins. Individual Dilps are found in different tissues and not all appear to be neurosecretory (Brogiolo et al, 2001). In the African malaria mosquito, Anopheles gambiae, there are five putative insulin-like peptides (Riehle et al, 2002) and in the yellow fever mosquito, Aedes aegypti, there are eight putative insulin-like peptides at least three of which are produced in the brain (Riehle et al, 2006).…”

Section: Insulin-like Proteins In Insectsmentioning

confidence: 99%

“…The insulin receptor has been shown to have an integral role in growth as well as in the assessment of nutritional state. It has been shown that the insulin receptor is a positive regulator of growth (Chen et al, 1996;Brogiolo et al, 2001). Insulin receptor transcription has also been shown to be nutritionally regulated.…”

Section: Introductionmentioning

confidence: 99%

“…If PI3K is mutated so that it cannot interact with IRS proteins (known as Chico in D. melanogaster), growth is reduced (Oldham et al, 2002). In contrast, when the genes that encode Drosophila insulin-like peptides (Dilps) are overexpressed, the flies show increased body size (Brogiolo et al, 2001). Furthermore, the overexpression of dFOXO, which is normally repressed through phosphorylation by PKB/Akt, decreases organ size and increases relative amounts of transcript of both Drosphila insulin receptor and 4EBP (Puig et al, 2003).…”

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Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Walsh

Smith

2011

Journal of Insect Physiology

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The tobacco hornworm, Manduca sexta, has been a useful model for studying insect endocrinology. In M. sexta the majority of growth occurs during the fifth (final) larval stage. This growth is concurrent with endocrine changes that lead to a metamorphic molt. Past research has focused on the interplay of three growth hormones: juvenile hormone (JH), prothoracicotropic hormone (PTTH) and ecdysone, in regulating metamorphosis. The prothoracic glands, source of ecdysteroid molting hormones in insects, play a crucial role in coordinating growth. Insulin/insulin-like growth factor (IGF) signaling has been shown to regulate growth and secretion of steroidogenic tissues in both vertebrates and invertebrates, but it had yet to be well-characterized in M. sexta.In this dissertation I examined the role of insulin-directed growth in prothoracic glands during both normal larval development and in response to nutrient deprivation. In particular, I predicted that in response to a reduction in nutrients, the prothoracic glands would stop growing and ecdysone secretion would be reduced. Changes were assessed in actin abundance and in two nutritionally sensitive transcripts, insulin receptor and 4EBP.Actin abundance in prothoracic glands increased in the first four days of this stage, demo nstrating significant growth. Actin decreased in glands from starved larvae, indicating a cessation of growth. Both insulin receptor and 4EBP transcript were present during normal larval development. As expected, both insulin receptor and 4EBP transcript increased in response to starvation. This research was the first demonstration of insulin signaling in prothoracic glands of fifth instar M. sexta larvae, and revealed nutritional sensitivity of the prothoracic glands. 5Finally, ecdysone assays were conducted to determine the impact of nutrition on glandular secretory capacity. Starved larvae were unable to secrete as much ecdysone as fed controls. Injections of insulin were unable to rescue the ability of the glands to secrete high levels of ecdysone. This demonstrated that although insulin signaling was correlated with normal growth of the glands, insulin is not sufficient to impact the ability of the glands to secrete ecdysone in the absence of nutrie nts. 6 This thesis is dedicated to my parents,Robert and Angela Walsh, whose love and support made this dissertation possible.

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Section: Insulin-like Proteins In Insectsmentioning

confidence: 99%

Section: Insulin-like Proteins In Insectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Walsh

Smith

2011

Journal of Insect Physiology

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“…Nos travaux récents chez la drosophile font le lien entre ces deux modes de régulation et démontrent que la voie TOR est à l'origine d'un contrôle humoral de la croissance par la nutrition. Chez la drosophile, comme chez la plupart des insectes holométaboles 1 [9]. Des études d'ablation spécifique ont montré que l'activité sécrétrice de ces neurones est nécessaire à la croissance globale de l'organisme [10].…”

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Les mouches gardent la ligne : slimfast, le corps gras et le contrôle humoral de la croissance

2004

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> Tous les organismes vivants croissent. Ils trouvent dans leur environnement des substances nutritives, les ingèrent, se développent et prolifèrent. Mais la qualité nutritive de l'environnement peut changer, obligeant les organismes à percevoir ces variations et à y répondre. Ainsi, les levures règlent leur croissance en fonction de la disponibilité en nutriments dans le milieu extracellulaire, via un module de signalisation remarquablement conservé faisant intervenir la protéine kinase TOR (target of rapamycin) [1]. La même kinase TOR est inhibée dans les cellules de mammifères cultivées in vitro lorsqu'elles sont transférées dans un milieu ne contenant pas d'acides aminés, et la synthèse protéique est immédiatement arrêtée [2]. Ces mécanismes de régulation intrinsèques à la cellule sont clairement éta-blis, cependant leur utilisation dans le contexte physiologique de la croissance d'un organisme composé de millions de cellules est encore largement inconnue. Chez les métazoaires, des circuits de régulations humorales, contrôlés par des molécules circulantes comme l'insuline ou les IGF (insulin-like growth factors) permettent d'harmoniser le métabolisme et la croissance des différents organes en fonction des conditions nutritionnelles. Nos travaux récents chez la drosophile font le lien entre ces deux modes de régulation et démontrent que la voie TOR est à l'origine d'un contrôle humoral de la croissance par la nutrition. Chez la drosophile, comme chez la plupart des insectes holométaboles 1 , la taille de l'adulte ne varie pas et est déterminée par une période de croissance spectaculaire qui prend place au cours des stades larvaires. Figure 2. Un modèle de régulation humorale de la croissance chez la drosophile. La stabilisation des Dilp via l'expression de dALS par le corps gras permettrait de moduler la croissance de la larve en fonction des conditions nutritionnelles.2 Tissus imaginaux : masses cellulaires indifférenciées apparaissant pendant l'embryogenèse et à l'origine de la formation de l'adulte. 3 Histolyse : destruction des organes par des hydrolases qui provoquent l'autolyse des cellules concernées ; des cellules phagocytaires vont absorber les débris.

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Drosophila – a Model System for Targets and Lead Identification in Cancer and Metabolic Disorders

Schütt¹,

Froesch²,

Hafen³

2003

Model Organisms in Drug Discovery

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An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control

Abstract: This study shows that the Drosophila insulin receptor autonomously controls cell and organ size, and that overexpression of a gene encoding an insulin-like peptide is sufficient to increase body size.

Cited by 1,133 publications

References 43 publications

Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Nutritional sensitivity of fifth instar prothoracic glands in the tobacco hornworm, Manduca sexta

Les mouches gardent la ligne : slimfast, le corps gras et le contrôle humoral de la croissance

Drosophila – a Model System for Targets and Lead Identification in Cancer and Metabolic Disorders

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