Mode of action of neuropeptides from the adipokinetic hormone family

GÄde, Gerd; Auerswald, Lutz

doi:10.1016/s0016-6480(03)00159-x

Cited by 222 publications

(161 citation statements)

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“…Starvationinduced mobilization of lipids in Rhodnius prolixus has been recently shown to be dependent on the AKH receptor (AlvesBezerra et al 2015). Given the hyperglycemic and hyperlipaemic effects of AKH in adult insects subjected to negative energy balance (Gäde and Auerswald 2003;Van Der Horst 2003;Lorenz and Gäde 2009), we studied Drosophila AKH functions during starvation. Akh A , Akh AP , AkhR 1 mutants were considerably more resistant to starvation than their genetically matched controls.…”

Section: Roles Of Akh In the Starvation Responsementioning

confidence: 99%

“…This induces TG and glycogen breakdown, which leads to the production and release of circulating carbohydrates (trehalose and glucose), lipids [diacylglycerides (DGs)], proline, or a combination of these fuel molecules, depending on the species`preference. Despite the divergence in the preferred type of circulating fuel, the role of AKH in the mobilization of energy stores is evolutionarily conserved among insects (reviewed in Gäde and Auerswald 2003;Lorenz and Gäde 2009). Consistently, AKH was identified as the hyperglycemic hormone in cockroaches (Steele 1961), as the hyperlipaemic hormone in Locusta (Beenakkers 1969;Mayer and Candy 1969) and as the hyperprolinaemic hormone in the fruit beetle Pachnoda sinuata (Auerswald and Gäde 1999).…”

mentioning

confidence: 99%

“…fuel, the role of AKH in the mobilization of energy stores is evolutionarily conserved among insects (reviewed in Gäde and Auerswald 2003;Lorenz and Gäde 2009). Consistently, AKH was identified as the hyperglycemic hormone in cockroaches (Steele 1961), as the hyperlipaemic hormone in Locusta (Beenakkers 1969;Mayer and Candy 1969) and as the hyperprolinaemic hormone in the fruit beetle Pachnoda sinuata (Auerswald and Gäde 1999).…”

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Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

et al. 2015

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Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation.KEYWORDS Drosophila; adipokinetic hormone; adipokinetic hormone precursor-related peptide; energy homeostasis; stress resistance E NERGY homeostasis requires continuous compensation for fluctuations in the energy expenditure and availability of food resources. Organisms thus build up reserves under positive energy balance and catabolize them when the balance turns negative to retain stable levels of circulating energy fuel. Insulin signaling induces the uptake of excessive circulating sugars, thus promoting reserve accumulation (reviewed, e.g., in Saltiel and Kahn 2001; Cohen 2006), whereas energy mobilization is under the control of glucagon and glucocorticoid signaling in mammals (reviewed, e.g., in Rui 2014;Charron and Vuguin 2015) and adipokinetic hormone (AKH) signaling in insects (reviewed, e.g., in Van der Horst 2003;Lorenz and Gäde 2009;Bednářová et al. 2013a). Consistent with their fundamental physiological function in energy mobilization, AKHs are found not only in insects, but are common in Protostomia, where they have been identified both in Ecdyszoa (in Arthropoda, Tardigrada, and Priapulida) and Lophotrochozoa (in Mollusca, Rotifera, and Annelida) (Gäde 2009;Hauser and Grimmelikhuijzen 2014). Nevertheless, physiological functions of AKHs have been studied mainly in Arthropoda. Similar to mammals, also insects store lipids in the form of triacylglycerides (TGs) and as carbohydrates in the form of glycogen. The main storage organ for lipid and glycogen in insects is the fat body, which can thus b...

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Section: Roles Of Akh In the Starvation Responsementioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

et al. 2015

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“…In many insects, there is variation in the numbers and primary sequences of different forms of AKH (Gäde and Auerswald 2003). In Drosophila, there is a single AKH, which is an octamer, possesses a pyroglutamine residue at its N terminus, and is amidated (Schaffer et al 1990).…”

mentioning

confidence: 99%

“…Specifically, the loss of AKH cells leads to an increased survival when these flies are challenged with starvation conditions and an absence of starvation-induced hyperactive behaviors (Lee and Park 2004;Isabel et al 2005). AKH has been hypothesized to be the functional equivalent of mammalian glucagon (Kim and Rulifson 2004), as it has been shown to be the primary insect hormone responsible for energy mobilization (Gäde and Auerswald 2003).…”

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confidence: 99%

Energy-Dependent Modulation of Glucagon-Like Signaling inDrosophilavia the AMP-Activated Protein Kinase

Braco¹,

Gillespie²,

Alberto³

et al. 2012

Genetics

102

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Adipokinetic hormone (AKH) is the equivalent of mammalian glucagon, as it is the primary insect hormone that causes energy mobilization. In Drosophila, current knowledge of the mechanisms regulating AKH signaling is limited. Here, we report that AMP-activated protein kinase (AMPK) is critical for normal AKH secretion during periods of metabolic challenges. Reduction of AMPK in AKH cells causes a suite of behavioral and physiological phenotypes resembling AKH cell ablations. Specifically, reduced AMPK function increases life span during starvation and delays starvation-induced hyperactivity. Neither AKH cell survival nor gene expression is significantly impacted by reduced AMPK function. AKH immunolabeling was significantly higher in animals with reduced AMPK function; this result is paralleled by genetic inhibition of synaptic release, suggesting that AMPK promotes AKH secretion. We observed reduced secretion in AKH cells bearing AMPK mutations employing a specific secretion reporter, confirming that AMPK functions in AKH secretion. Live-cell imaging of wild-type AKH neuroendocrine cells shows heightened excitability under reduced sugar levels, and this response was delayed and reduced in AMPK-deficient backgrounds. Furthermore, AMPK activation in AKH cells increases intracellular calcium levels in constant high sugar levels, suggesting that the underlying mechanism of AMPK action is modification of ionic currents. These results demonstrate that AMPK signaling is a critical feature that regulates AKH secretion, and, ultimately, metabolic homeostasis. The significance of these findings is that AMPK is important in the regulation of glucagon signaling, suggesting that the organization of metabolic networks is highly conserved and that AMPK plays a prominent role in these networks.

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Endocrine Control of Oxidative Stress in Insects

Krishnan

Kodrı́k

2011

Oxidative Stress in Vertebrates and Invertebrates

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Mode of action of neuropeptides from the adipokinetic hormone family

Cited by 222 publications

References 78 publications

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants

Energy-Dependent Modulation of Glucagon-Like Signaling inDrosophilavia the AMP-Activated Protein Kinase

Endocrine Control of Oxidative Stress in Insects

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