Aminergic and peptidergic modulation of Insulin-Producing Cells in Drosophila DOI Creative Commons
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

eLife, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila - population insulin-producing cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based 'intrinsic pharmacology' approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system Drosophila.

Language: Английский

The Regulation of Drosophila Sleep DOI Creative Commons
Orie T. Shafer, Alex C. Keene

Current Biology, Journal Year: 2021, Volume and Issue: 31(1), P. R38 - R49

Published: Jan. 1, 2021

Language: Английский

Citations

166
Hormonal axes in Drosophila: regulation of hormone release and multiplicity of actions DOI Creative Commons
Dick R. Nässel, Meet Zandawala

Cell and Tissue Research, Journal Year: 2020, Volume and Issue: 382(2), P. 233 - 266

Published: Aug. 22, 2020

Hormones regulate development, as well many vital processes in the daily life of an animal. Many these hormones are peptides that act at a higher hierarchical level animal with roles organizers globally orchestrate metabolism, physiology and behavior. Peptide can on multiple peripheral targets simultaneously convey basal states, such metabolic status sleep-awake or arousal across central neuronal circuits. Thereby, they coordinate responses to changing internal external environments. The activity neurosecretory cells is controlled either by (1) cell autonomous sensors, (2) other neurons relay signals from sensors tissues (3) feedback target cells. Thus, hormonal signaling axis commonly comprises several components. In mammals vertebrates, axes known, hypothalamic-pituitary-gonad hypothalamic-pituitary-thyroid reproduction respectively. It has been proposed basic organization evolutionarily old cellular homologs hypothalamic-pituitary system be found for instance insects. To obtain appreciation similarities between insect vertebrate axes, we review systems Drosophila. Our outlines major peptidergic pathways known Drosophila presents set schemes orchestrating systems. detailed larval adult displays only very those arthropods vertebrates.

Language: Английский

Citations

89
Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions DOI Creative Commons
Dick R. Nässel, Meet Zandawala

Open Biology, Journal Year: 2022, Volume and Issue: 12(7)

Published: July 1, 2022

Plasticity in animal behaviour relies on the ability to integrate external and internal cues from changing environment hence modulate activity synaptic circuits of brain. This context-dependent neuromodulation is largely based non-synaptic signalling with neuropeptides. Here, we describe select peptidergic systems Drosophila brain that act at different levels a hierarchy associated physiology. These regions, such as central complex mushroom bodies, which supervise specific behaviours. At top level there are small numbers large neurons arborize widely multiple areas orchestrate or global state manner. bottom local provide executive sensory gain intrinsically restricted parts neuronal circuits. The orchestrating receive interoceptive signals mediate energy sleep homeostasis, metabolic circadian timing, well affect food search, aggression mating. Some these can be triggers conflicting behaviours mating versus aggression, feeding, participate circuits, enabling choices switches.

Language: Английский

Citations

55
A gut-secreted peptide suppresses arousability from sleep DOI Creative Commons
Iris Titos, Alen Juginović, Alexandra Vaccaro

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1382 - 1397.e21

Published: March 1, 2023

Language: Английский

Citations

37
Aminergic and peptidergic modulation of Insulin-Producing Cells in Drosophila DOI Open Access
Martina Held, Rituja S Bisen, Meet Zandawala

et al.

Published: Feb. 10, 2025

Insulin plays a critical role in maintaining metabolic homeostasis. Since demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments mediated by different pathways, most prominently the blood glucose level, but also feedforward signals from motor circuits and neuromodulatory systems. Here, we analyze how inputs control activity of main source Drosophila – population Insulin-Producing Cells (IPCs) located brain. IPCs functionally analogous mammalian pancreatic beta cells, their location makes them accessible for vivo recordings intact animals. We characterized functional using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, an optogenetics-based ‘intrinsic pharmacology’ approach. Our results show that IPC expresses variety receptors neuromodulators classical neurotransmitters. Interestingly, exhibit heterogeneous profiles, suggesting can modulated differentially. This is supported electrophysiological IPCs, which performed while activating populations modulatory neurons. analysis revealed some have effects on activity, such they inhibit one subset exciting another. Monitoring calcium across uncovered these responses occur simultaneously. Certain shifted towards excited state, others it inhibition. Taken together, provide comprehensive, multi-level neuromodulation insulinergic system .

Language: Английский

Citations

1
Drosophila insulin‐like peptides: from expression to functions – a review DOI Open Access
Uliana Semaniuk,

Veronika Piskovatska,

Olha Strilbytska

et al.

Entomologia Experimentalis et Applicata, Journal Year: 2020, Volume and Issue: 169(2), P. 195 - 208

Published: Oct. 9, 2020

Abstract Insulin‐like peptides (ILPs) belong to the insulin superfamily and act as hormones, neuromediators, growth factors during post‐embryonic life‐cycle stages of insects. These are encoded by different genes in various species. In genus Drosophila , eight known, seven which likely bind receptor, whereas DILP8 is a known ligand Lgr3 receptor. Binding DILPs 1‐7 receptors leads activation intracellular proteins related conserved insulin/IGF (insulin‐like factors) signaling pathway. The pathway acts within complex physiological regulatory network involved coordination development, growth, behavior, metabolism, lifespan, cognitive functions current review summarizes recent data about structure function ILPs fruit flies. role environmental genetic manipulations modulating their association with lifespan metabolism assessed. Further investigation identification pharmacological or biotechnological interventions that may decrease could be highly promising approach for extension human health span longevity.

Language: Английский

Citations

52
An overview of the insulin signaling pathway in model organisms Drosophila melanogaster and Caenorhabditis elegans DOI

Sanaz G. Biglou,

William G. Bendena, Ian D. Chin-Sang

et al.

Peptides, Journal Year: 2021, Volume and Issue: 145, P. 170640 - 170640

Published: Aug. 24, 2021

Language: Английский

Citations

51
Loss of UCHL1 rescues the defects related to Parkinson’s disease by suppressing glycolysis DOI Creative Commons
Su Jin Ham, D. S. Lee,

Wen Jun Xu

et al.

Science Advances, Journal Year: 2021, Volume and Issue: 7(28)

Published: July 9, 2021

Loss of UCHL1 activates an energy-dependent mitophagy via pyruvate kinase, which relieves Parkinson’s disease symptoms.

Language: Английский

Citations

43
Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity DOI Creative Commons
Jason W. Millington, George P. Brownrigg,

Charlotte F. Chao

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 15, 2021

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work Drosophila showed that was higher females, yet mechanisms underlying increased female remain unclear. Here, we discover a protein-rich diet augments females and not males because of female-biased increase activity conserved insulin/insulin-like growth factor signaling pathway (IIS). This sex-biased upregulation IIS triggered by diet-induced stunted mRNA required insulin-like peptide 2 , illuminating new sex-specific roles for these genes. Importantly, show sex determination gene transformer promotes via transcriptional coactivator Spargel to regulate male-female difference plasticity. Together, findings provide vital insight into nutrient-dependent

Language: Английский

Citations

41
Decoding the nexus: branched-chain amino acids and their connection with sleep, circadian rhythms, and cardiometabolic health DOI Creative Commons
Hui Li, Laurent Seugnet

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1350 - 1363

Published: June 3, 2024

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and, either directly or indirectly, overall body health, encompassing metabolic and cardiovascular well-being. Given the heightened activity of brain, there exists a considerable demand nutrients in comparison to other organs. Among these, branched-chain amino acids, comprising leucine, isoleucine, valine, display distinctive significance, from their contribution protein structure involvement metabolism, especially cerebral processes. first acids that are released into circulation post-food intake, assume pivotal role regulation synthesis, modulating insulin secretion acid sensing pathway target rapamycin. Branched-chain key players influencing brain’s uptake monoamine precursors, competing shared transporter. Beyond these contribute cycles γ-aminobutyric glutamate, well energy metabolism. Notably, they impact GABAergic neurons excitation/inhibition balance. rhythmicity plasma concentrations, observed over 24-hour conserved rodent models, is under circadian clock control. mechanisms underlying those rhythms physiological consequences disruption not fully understood. Disturbed sleep, obesity, diabetes, diseases can elevate concentrations modify oscillatory dynamics. driving effects currently focal point ongoing research efforts, since normalizing levels has ability alleviate severity pathologies. In this context, Drosophila model, though underutilized, holds promise shedding new light on mechanisms. Initial findings indicate its potential introduce novel concepts, particularly elucidating intricate connections between clock, sleep/wake, Consequently, use transport emerge critical components orchestrators web interactions across multiple organs throughout sleep/wake cycle. They could represent one so far elusive connecting sleep patterns paving way therapeutic interventions.

Language: Английский

Citations

8