A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila

Oh, Yangkyun; Lai, Jason Sih-Yu; Mills, Holly; Erdjument‐Bromage, Hediye; Giammarinaro, Benno; Saadipour, Khalil; Wang, Justin G.; Farhan, Abu; Neubert, Thomas A.; Suh, Greg S.B.

doi:10.1038/s41586-019-1675-4

Cited by 106 publications

(145 citation statements)

References 45 publications

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“…Unsurprisingly, the most abundant neuropeptide receptor in AKH cells is the AstA-R1 receptor ( Figure 1A), which had previously been reported to be an upstream regulator of AKH release (Hentze et al, 2015). Likewise, previous publications had implicated that the peptide Myosuppressin as an inhibitor of AKH secretion in different insects (Vullings et al, 1998), as well as the sNPF receptor (Oh et al, 2019). Thus, our analysis of the transcriptome shows consistency with previous behavioral results.…”

Section: Akh Cells Express Multiple Receptor Moleculessupporting

confidence: 90%

Modulation of metabolic hormone signalingviaa circadian hormone and a biogenic amine inDrosophila melanogaster

Braco

Saunders

Nelson

et al. 2020

Preprint

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In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified AKH’s role in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-expressing cell transcriptome to identify potential regulatory elements controlling AKH cell activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors, dopamine ecdysone receptor (DopEcR), Dopamine 2-like receptor (D2R), Dopamine 1-like receptor 2 (DopR2), DopR, and the Pigment Dispersing Factor (PDFR). We tested the consequences of targeted genetic knockdown and found that RNAi elements targeting each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in AKH cells resulted in a significantly shorter lifespan during starvation. These manipulations also caused various changes in locomotor activity under starvation. Specifically, there were higher amounts of locomotor activity in dopamine receptor knockdowns, in both replete and starved states. PDFR knockdown resulted in increased locomotion during replete conditions and locomotion levels that were comparable to wild-type during starvation. Expression of a membrane-tethered PDF led to decreased locomotion under baseline and starvation. Next, we used live-cell imaging to evaluate the acute effects of the ligands for these receptors (dopamine, ecdysone, and Pigment Dispersing Factor) on AKH cell activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, we found that co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones are acting antagonistically. We also found that PDF application directly led to an increase in cAMP in AKH cells, and that this response was dependent on expression of the PDFR in AKH cells. Together these results suggest a complex circuit in which multiple hormones act on AKH cells to modulate metabolic state.

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Section: Akh Cells Express Multiple Receptor Moleculessupporting

confidence: 90%

Modulation of metabolic hormone signalingviaa circadian hormone and a biogenic amine inDrosophila melanogaster

Braco

Saunders

Nelson

et al. 2020

Preprint

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“…Although the nutritional cues conveyed by sNPF are not clear, Drosophila sNPF regulates feeding like its mammalian homolog neuropeptide Y (NPY) (Lee et al 2004;Root et al 2011;Carlsson et al 2013;Ko et al 2015;Selcho et al 2017), which suggests that this neuromodulatory peptide may link feeding behavior with systemic growth control. In the adult brain, a pair of sugar-sensing neurons sense sugar levels and release sNPF onto both the IPCs and the APCs, activating the former and inhibiting the latter, and thus coordinating the uptake and usage of energetic species with their storage or release (Oh et al 2019).…”

Section: Regulation Of Ipc Activity and Functional Role Of Dilpsmentioning

confidence: 99%

“…However, IPCs do not express sNPF-R-GAL4;Kapan et al (2012); Carlsson et al (2013) (same line in both).IPCs express sNPF-R-GAL4;Kapan et al (2012). sNPF from sugar-sensitive upstream neurons activates the IPCs and inhibits the APCs via sNPF-R;Oh et al (2019). sNPF from clock neurons increases cAMP and Ca 2+ levels, likely directly, to block dormancy;Nagy et al (2019).…”

mentioning

confidence: 99%

Regulation of Body Size and Growth Control

Texada¹,

Kaburagi²,

Rewitz³

2020

Genetics

116

146

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The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by Drosophila insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made Drosophila a prime model for understanding the coordination of growth and maturation in animals.

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“…Another peptide that has been shown to modulate both DILP and Akh signaling is sNPF, which is secreted from certain neurons of the brain in larvae and adults. In response to starvation, sNPF release upregulates feeding and DILPgene expression (in anticipation of new nutrients) through the sNPF receptor (sNPF-R) in the IPCs, which is coupled to stimulatory G-proteins in these cells [219][220][221][222][223][224]. In a feedback arrangement, sNPF-positive neurons also express InR and, in response to DILP signaling, produce more sNPF to promote continued feeding.…”

Section: Signals That Regulate Both the Ipcs And Apcs To Mediate Nutrmentioning

confidence: 99%

Metabolism and growth adaptation to environmental conditions in Drosophila

Kaburagi

Texada

Halberg

et al. 2020

Cell. Mol. Life Sci.

104

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Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major influences on growth and final adult body size in animals. This developmental plasticity depends on adaptive responses to internal state and external cues that are essential for developmental processes. Genetic studies have shown that the fruit fly Drosophila, similarly to mammals, regulates its metabolism, growth, and behavior in response to the environment through several key hormones including insulin, peptides with glucagon-like function, and steroid hormones. Here we review emerging evidence showing that various environmental cues and internal conditions are sensed in different organs that, via inter-organ communication, relay information to neuroendocrine centers that control insulin and steroid signaling. This review focuses on endocrine regulation of development, metabolism, and behavior in Drosophila, highlighting recent advances in the role of the neuroendocrine system as a signaling hub that integrates environmental inputs and drives adaptive responses.

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A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila

Cited by 106 publications

References 45 publications

Modulation of metabolic hormone signalingviaa circadian hormone and a biogenic amine inDrosophila melanogaster

Modulation of metabolic hormone signalingviaa circadian hormone and a biogenic amine inDrosophila melanogaster

Regulation of Body Size and Growth Control

Metabolism and growth adaptation to environmental conditions in Drosophila

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