Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11

Ugrankar, Rupali; Theodoropoulos, Pano; Akdemir, Fatma; Graff, Jonathan M.

doi:10.1038/s42003-018-0109-4

Cited by 34 publications

(27 citation statements)

References 72 publications

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“…While Dilp1, Dilp2, Dilp3 and Dilp5 are all produced by the IPCs, previous studies have uncovered significant differences in regulation, secretion, and phenotypic effects of these IPC-derived Dilps (Brogiolo et al, 2001;Zhang et al, 2009;Okamoto et al, 2009;Grönke et al, 2010;Cognigni et al, 2011;Stafford et al, 2012;Bai et al, 2012;Linneweber et al, 2014;Cong et al, 2015;Liu et al, 2016;Nässel & Vanden Broeck, 2016;Post et al, 2018Post et al, , 2019Semaniuk et al, 2018;Ugrankar et al, 2018;Brown et al, 2020). We therefore wanted to determine the individual contributions of IPC-derived Dilps to body size in each sex.…”

Section: Loss Of Individual Dilp Genes Causes a Female-specific Decrementioning

confidence: 99%

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects onDrosophilabody size

Millington

Brownrigg

Basner-Collins

et al. 2020

Preprint

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In Drosophila, female body size is approximately 30% larger than male body size due to an increased rate of larval growth. While the mechanisms that control this sex difference in body size remain incompletely understood, recent studies suggest that the insulin/insulin-like growth factor signaling pathway (IIS) plays a role in the sex-specific regulation of growth during development. In larvae, IIS activity differs between the sexes, and there is evidence of sex-specific regulation of IIS ligands. Yet, we lack knowledge of how changes to IIS activity impact growth in each sex, as the majority of studies on IIS and body size use single- or mixed-sex groups of larvae and/or adult flies. The goal of our current study was to clarify the requirement for IIS activity in each sex during the larval growth period. To achieve this goal we used established genetic approaches to enhance, or inhibit, IIS activity, and quantified body size in male and female larvae. Overall, genotypes that inhibited IIS activity caused a female-biased decrease in body size, whereas genotypes that augmented IIS activity caused a male-specific increase in body size. This data extends our current understanding of larval growth by showing that most changes to IIS pathway activity have sex-biased effects on body size, and highlights the importance of analyzing data by sex in larval growth studies.

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Section: Loss Of Individual Dilp Genes Causes a Female-specific Decrementioning

confidence: 99%

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects onDrosophilabody size

Millington

Brownrigg

Basner-Collins

et al. 2020

Preprint

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show abstract

“…In the literature, changes of insulin level and insulin signaling in AD brains are still debated and inconsistent 26 . By using RT-PCR analyses, we found that the head level of thor ( 4EBP homolog in the fly ) , which is reduced by insulin 27 , was decreased in Aβ flies (Fig. 3a); the level of head tobi (target of brain insulin) was increased in Aβ flies (Fig.…”

Section: Resultsmentioning

confidence: 99%

Insulin signaling in Drosophila melanogaster mediates Aβ toxicity

et al. 2019

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Alzheimer’s disease (AD) and diabetes are clinically positively correlated. However, the connection between them is not clarified. Here, using Drosophila as a model system, we show that reducing insulin signaling can effectively suppress the toxicity from Aβ (Amyloid beta 42) expression. On the other hand, Aβ accumulation led to the elevation of fly insulin-like peptides (ILPs) and activation of insulin signaling in the brain. Mechanistically, these observations are attributed to a reciprocal competition between Drosophila insulin-like peptides and Aβ for the activity of insulin-degrading enzyme (IDE). Intriguingly, peripheral insulin signaling is decreased despite its heightened activity in the brain. While many upstream factors may modify Aβ toxicity, our results suggest that insulin signaling is the main downstream executor of Aβ damage, and thus may serve as a promising target for Alzheimer’s treatment in non-diabetes patients. This study explains why more Alzheimer’s cases are found in diabetes patients.

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“…Sugar consumption is regulated depending on the satiation state of the animal. In Drosophila larvae, hemolymph carbohydrate levels negatively correlate with sucrose consumption [27].…”

Section: Sucrose Consumption Specifically Suppresses Larmmentioning

confidence: 99%

Insulin signaling represents a gating mechanism between different memory phases in Drosophila larvae

et al. 2020

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The ability to learn new skills and to store them as memory entities is one of the most impressive features of higher evolved organisms. However, not all memories are created equal; some are short-lived forms, and some are longer lasting. Formation of the latter is energetically costly and by the reason of restricted availability of food or fluctuations in energy expanses, efficient metabolic homeostasis modulating different needs like survival, growth, reproduction, or investment in longer lasting memories is crucial. Whilst equipped with cellular and molecular pre-requisites for formation of a protein synthesis dependent long-term memory (LTM), its existence in the larval stage of Drosophila remains elusive. Considering it from the viewpoint that larval brain structures are completely rebuilt during metamorphosis, and that this process depends completely on accumulated energy stores formed during the larval stage, investing in LTM represents an unnecessary expenditure. However, as an alternative, Drosophila larvae are equipped with the capacity to form a protein synthesis independent so-called larval anaesthesia resistant memory (lARM), which is consolidated in terms of being insensitive to cold-shock treatments. Motivated by the fact that LTM formation causes an increase in energy uptake in Drosophila adults, we tested the idea of whether an energy surplus can induce the formation of LTM in the larval stage. Suprisingly, increasing the metabolic state by feeding Drosophila larvae the disaccharide sucrose directly before aversive olfactory conditioning led to the formation of a protein synthesis dependent longer lasting memory. Moreover, formation of this memory component is accompanied by the suppression of lARM. We ascertained that insulin receptors (InRs) expressed in the mushroom body Kenyon cells suppresses the formation of lARM and induces the formation of a protein synthesis dependent longer lasting memory in Drosophila larvae. Given the numerical simplicity of the larval nervous system this work offers a unique prospect to study the impact of insulin signaling on the formation of protein synthesis dependent memories on a molecular level.

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Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11

Cited by 34 publications

References 72 publications

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects onDrosophilabody size

Genetic manipulation of insulin/insulin-like growth factor signaling pathway activity has sex-biased effects onDrosophilabody size

Insulin signaling in Drosophila melanogaster mediates Aβ toxicity

Insulin signaling represents a gating mechanism between different memory phases in Drosophila larvae

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