Adipokinetic Hormone - an overview | ScienceDirect Topics

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Skip to Main contentScienceDirectJournals BooksRegisterSign in Sign inRegisterJournals BooksHelpAdipokinetic HormoneAdipokinetic hormones (AKHs) are a family of neuropeptides that consist of 8–10 amino acids and have a C-terminus blocked by pyroglutamate and an N-terminus blocked by an amide group.From: Advances in Insect Physiology, 2014Related terms:PeptideLipidsHormonesLocustsProteinsHemolymphDiacylglycerolsCorpora cardiacaView all TopicsDownload as PDFSet alertAbout this pageAdipokinetic Hormones: Structure and BiosynthesisRob C.H.M. Oudejans, Dick J. Van der Horst, in Encyclopedia of Hormones, 2003III Biosynthesis of adipokinetic hormonesAll AKHs studied thus far are translated from separate mRNAs. They code for preprohormones with a simple structure: a signal sequence, a monocopy AKH sequence (starting with a Gln to form pGlu), a Gly residue (to form the terminal AKH amide group), a dibasic processing site, and an AKH-associated peptide sequence. In particular, in L. migratoria the signal sequences of the three preprohormones are cotranslationally cleaved, and the resulting prohormones of AKH-I and -II dimerize at random by oxidation of their Cys residues and give rise to two homodimeric precursor molecules (AKH-I/I and AKH-II/II) and one heterodimeric precursor molecule (AKH-I/II). This dimerization is a rather unique phenomenon, first established for another locust species (S. gregaria). Further proteolytic processing of the dimeric products in the secretory granules of the AKH cells of the corpus cardiacum results in the bioactive hormones and one heterodimeric and two homodimeric AKH-precursor-related peptides (APRPs) with as yet unknown functions (see Fig. 1). The biosynthesis of AKH-III is not yet fully understood. Recently, dimerization of the AKH-III prohormone with itself (it contains two Cys residues itself) has been established. Dimerization with the prohormones of AKH-I and -II has not been observed, and whether a cyclic prohormone of AKH-III can arise by formation of an internal disulfide bond is unknown.Figure 1. The biosynthesis of the locust adipokinetic hormones AKH-I and -II and the adipokinetic precursor-related peptides APRP-1, -2, and -3. After cleavage of the signal peptide from the preprohormones, the resulting monomeric prohormones, which consist of the AKH sequence and the AKH-associated peptide (AAP), form three dimeric prohormones, which are then processed to the AKHs and the APRPs.In vitro studies on the biosynthesis of AKHs in locusts have revealed that the total time required for their biosynthesis from the starting point when radiolabeled amino acids are made available to the moment that radiolabeled bioactive hormones appear is 30–60 min. In L. migratoria the time for biosyn-thesis of AKH-III is shorter than that for AKH-I and -II, suggesting that there are two different pathways or different processing procedures for AKH-I/II, on the one hand, and for AKH-III, on the other.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B0123411033000073Adipokinetic HormoneShinji Nagata, in Handbook of Hormones, 2016StructureStructural FeaturesMost AKH/RPCHs are octapeptides with an N-terminal pyroGlu residue, C-terminal amidation, and two conserved aromatic amino acids at the fourth and eighth residues. Sequences of AKH and RPCH are highly conserved over arthropod species (Table 59.1).Table 59.1. Alignment of AKHs and RPCHGryllus bimaculatusAKHpEVNFSTW–NH2Drosophila melanogasterAKHpELTFSTGW–NH2Locusta migratoriaAKHpELNFTPNWGT–NH2AKH-IIpELNFSAGW–NH2AKH-IIIpELNFTPWW–NH2Pandalus borealisRPCHpELTFSTGW–NH2Structure and SubtypeAKH has been identified in more than 40 insect species, so far [4]. In most insect species, several AKH subtypes are present. In L. migratoria, two structurally related subtypes (AKH-II and -III) have been identified [5]. Some AKH subtypes are exceptionally nonapeptides and decapeptides. The number of subtypes differs according to species. No subtypes of crustacean RPCH are known.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B9780128010280000593Target Receptors in the Control of Insect Pests: Part IIHeleen Verlinden, ... Jozef Vanden Broeck, in Advances in Insect Physiology, 20143.2.4 Adipokinetic hormoneAdipokinetic hormones (AKHs) are a family of neuropeptides that consist of 8–10 amino acids and have a C-terminus blocked by pyroglutamate and an N-terminus blocked by an amide group. AKHs show significant structural similarity with the red pigment concentrating hormones (RPCHs) of crustaceans and thus these neuropeptides were grouped in the AKH/RPCH family (Gäde, 1997). AKH and RPCH are arthropod homologues of the vertebrate gonadotropin-releasing hormones (GnRH) family (De Loof et al., 2012). The first fully characterised AKH was isolated from the CC of L. migratoria and functions in lipid mobilisation during flight (Stone et al., 1976a,b). AKH probably is the most studied insect neuropeptide and over 50 members of this family have been characterised from an immensely diverse array of insect species ranging from Ephemeroptera and Odonata to Lepidoptera and Hymenoptera (Audsley et al., 2011; Gäde, 2009; Gäde and Marco, 2012; Gäde and Simek, 2010; Gäde et al., 2013; Jedlicka et al., 2012; Marco et al., 2013; Weaver et al., 2012; Zoephel et al., 2012). The most conserved amino acids in the peptide structure of AKH are Phe4, Trp8 and Gly9 (in AKHs longer than 8 amino acids) (Gäde, 1997). All AKHs are derived from precursor proteins containing a secretory signal peptide, one AKH and one AKH precursor-related peptide (APRP) (Gäde, 1997). When an insect contains multiple AKHs, multiple AKH precursor genes are encoded in the genome. Hitherto, no AKH precursor encoding multiple AKH peptides has been identified. AKHs are mainly synthesised and stored in the glandular lobes of the CC (Bogerd et al., 1995; Harthoorn et al., 1999; Stone and Mordue, 1979).The first AKH receptors to be cloned and deorphanised were those of D. melanogaster and B. mori (Park et al., 2002; Staubli et al., 2002). Numerous other AKH receptors were characterised afterwards and several studies have investigated the ligand-receptor interactions in detail (for a review, see: Caers et al., 2012). AKH is a central regulator of energy metabolism in insects. It is secreted by the CC into the hemolymph in conditions of intense skeletal muscle activity during energy demanding processes (such as flight) and regulates the mobilisation of energy reserves from the fat body. AKH can mobilise three different energy sources, partly depending on the process requiring energy and sometimes even on the insect s life stage: stored glycogen can be broken down to trehalose, lipids can be converted to diglycerides and proline can be used as an energy source as well. AKHs also inhibit energy demanding anabolic processes, such as protein and lipid biosynthesis, during periods of intense muscle activity (Arrese and Soulages, 2010; Lorenz and Gäde, 2009). Besides its main role as the pivotal energy regulating neuropeptide, AKH fulfils a number of other functions as well. A function of AKH that is linked to the energy balance was elucidated in G. bimaculatus. RNAi induced knockdown of the AKH receptor increased the frequency of feeding, but did not alter the amount of food taken up during each of these feeding cycles, resulting in an augmentation of the total food intake over multiple feeding cycles. This increased food intake was probably due to the lowered hemolymph titers of trehalose and diacylglycerol caused by the inability of AKH to bind enough receptors in the fat body and release sugars and lipids into circulation. The AKH receptor knockdown animals also seemed more resistant to starvation (Konuma et al., 2012). AKH might also have a function in starvation-induced foraging behaviour and absence of AKH extends survival time of starved flies because of a slower energy mobilisation rate (Isabel et al., 2005; Lee and Park, 2004). AKH titers in the hemolymph are affected by acute stress responses to toxic substances in the environment, like insecticides (Candy, 2002; Kodrík and Socha, 2005; Velki et al., 2011), herbicides (Kodrík et al., 2007; Vecera et al., 2007) or KCl (Candy, 2002), differences in light/dark cycle (Kodrík and Socha, 2005; Kodrík et al., 2005), bacterial proteins (Kodrík et al., 2007) and food compounds that induce formation of reactive oxygen species (ROS) in the insect (Vecera et al., 2012). AKH is able to counteract the effects of ROS in the insect body and even succeeds in preventing mortality caused by the oxidising effect of these molecules (Bednářová et al., 2013). Another function of AKH is associated with the female reproductive system: by the inhibition of anabolic processes in the fat body, AKH can lead to diminished levels of protein and lipids in this important energy storage organ and have an indirect, negative influence on egg development (Lorenz, 2003). Because AKH affects the titers of apolipophorin III in the hemolymph, it also exerts an indirect function on the insect s immune system (Adamo et al., 2008). Apolipophorin III functions in lipid transport and pathogen detection and uses the same binding sites for recognition of both lipids and lipopolysaccharides in these different physiological processes (Leon et al., 2006). The amount of free apolipophorin III in the hemolymph is reduced following an AKH injection due to the binding of free lipids that are released from the fat body. These reduced levels of free apolipophorin III in the hemolymph lead to immunosuppression (Adamo et al., 2008). AKH was able to augment insecticide induced mortality in a recent study: both oral and topical co-administration of the insecticide permethrin and AKH intensified the permethrin action and led to increased mortality. It is hypothesised that AKH induced elevation of metabolism leads to an enhanced penetration and insecticidal action of permethrin (Kodrík et al., 2010). This has been the only study on the possible effect of AKH where a combined strategy of pesticide application and neuropeptide action for pest insect control was used. AKH itself does not elicit insecticidal effects, but the vast knowledge of this neuropeptide, its receptor interaction and signalling pathway and its functions may aid in the successful application of AKH in combination with other insecticidal compounds to enhance their effect.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B9780124170100000033Adipokinetic Hormones: Structure and Biosynthesis☆G. Gäde, D.J. Van der Horst, in Reference Module in Neuroscience and Biobehavioral Psychology, 2017Storage, Release, and Inactivation of Adipokinetic HormonesAKHs are stored in the secretory granules of the adipokinetic cells of the corpus cardiacum. In L. migratoria the total content of the AKHs increases continuously during the larval stages and throughout adult life. In aging locusts an increasing number of intracisternal granules that contain stores of AKH prohormones/precursors are also found. The three AKHs, co-localized and stored in the same secretory granules, are released during flight (Harthoorn et al., 1999). Since the membrane of the pertinent secretory granule fuses with the plasma membrane, the total contents of the granule are released into the hemolymph: the bioactive AKHs, the APRPs, and possibly other end products.The release of the AKHs in L. migratoria is subjected to many regulatory substances, which are of either stimulatory or inhibitory nature and can be of both neural and humoral origin (Vullings et al., 1999; Flanigan and Gäde, 1999). A detailed description falls beyond the scope of this article. The only natural stimulus of release of the AKHs is flight and the relative contributions of all known substances effective in the release process remain to be established in vivo.The situation in L. migratoria is even more complex, since secretory granules of only a particular age can be released. Newly formed granules containing the AKHs must mature before they can release their contents (or before they can fuse with the plasma membrane). Granules more than 8 h old are believed to enter a non-releasable pool. Determination of the total hormone content of a neuroendocrine structure has therefore a limited physiological value, because only the releasable amount of hormone is relevant (Diederen et al., 2002; Harthoorn et al., 2002).Finally, the balance between released hormones (a mixture of many compounds present in the secretory granule) and the rate of their inactivation prior to reaching the target tissue will be of eminent importance for their ultimate effect. The three AKHs of L. migratoria appear to be inactivated differentially after their release, with half-lives during flight of 35, 37, and 3 min obtained for AKH-I, -II, and -III, respectively (Oudejans et al., 1996, 1999).View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B9780128093245033368Lipid Transport☆Dick J. Van der Horst, Robert O. Ryan, in Reference Module in Life Sciences, 2017Adipokinetic hormone receptorsBinding of the AKHs to their plasma membrane receptor(s) at the fat body cells is the primary step to the induction of signal transduction events that ultimately lead to the activation of target key enzymes and the mobilization of lipids as a fuel for flight. Although the AKHs constitute extensively studied neurohormones, and their actions have been shown to occur via G protein-coupled receptors (GPCRs) (for reviews, see Van Marrewijk and Van der Horst, 1998; Vroemen et al., 1998), the general properties of which are remarkably well conserved during evolution (for review, see Vanden Broeck, 2001), insect AKH receptors have been identified only recently. However, in L. migratoria, which produces three different AKHs and may be envisaged to have (three) different AKH receptors, the receptor(s) are as yet unidentified. The first insect AKH receptors characterized at the molecular level, namely those of D. melanogaster and the silkworm Bombyx mori (Staubli et al., 2002), were shown to be GPCRs structurally related to mammalian gonadotropin-releasing hormone (GnRH) receptors. No other AKH receptors were isolated until 2006, when an AKH receptor from the American cockroach Periplaneta americana was identified (Hansen et al., 2006); the production of two intrinsic AKHs (Periplaneta AKH-I and -II) may suggest the presence of a second AKH receptor. A similar cockroach AKH receptor was also identified by Wicher et al. (2006); there are, however, differences in one amino acid residue, as well as in the response towards the two Periplaneta AKHs (cf. Hansen et al., 2006). In the malaria mosquito Anopheles gambiae an AKH receptor has been characterized in addition to an orphan receptor, the close relationship of which to the insect AKH receptors identified thus far suggesting that this receptor is an AKH receptor as well (Belmont et al., 2006). For the yellow fever mosquito Aedes aegypti, two splice variants of the AKH receptor gene, differing at their C-terminal ends, were reported (Kaufmann et al., 2009); it was postulated that both receptor variants could selectively bind the two AKH peptides found in A. aegypti. The signaling of the AKH receptor of B. mori and its peptide ligands (Bombyx AKH1, −2 and −3) have been recently characterized at the molecular and functional levels (Zhu et al., 2009). Recent cloning studies demonstrating that the GnRH receptor in the nematode Caenorhabditis elegans is stimulated by both a C. elegans AKH-GnRH-like peptide and Drosophila AKH suggest that the AKH-GnRH signaling system arose very early in metazoan evolution (Lindemans et al., 2009).View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B9780128096338040450EndocrinologyD.A. Schooley, ... G.M. Coast, in Comprehensive Molecular Insect Science, 20053.10.2.1.3 AKH synthesis and releaseLike most neuropeptides, AKH is derived by processing of a larger precursor protein (Hekimi and O Shea, 1987). The steps involved in AKH synthesis have been most thoroughly characterized in S. gregaria (O Shea and Rayne, 1992), and subsequent studies in other insects have shown that the basic features of AKH biosynthesis are conserved. AKH precursor proteins share a similar organization, an N-terminal signal peptide, followed by AKH and the AKH precursor related peptide (APRP) (O Shea and Rayne, 1992), as first shown in S. gregaria (Schulz-Aellen et al., 1989) and M. sexta (Bradfield and Keeley, 1989). The locust AKH precursor exists as a dimer formed by oxidation of the Cys residues present in the APRP. This occurs prior to proteolytic processing in the trans-Golgi at basic amino acid residues and C-terminal amidation (Rayne and O Shea, 1994). The dimeric structure of the precursor might confer a conformation that facilitates or allows the correct processing of the precursor. Since multiple AKHs (Diederen et al., 1987; Hekimi et al., 1991) and their mRNAs (Bogerd et al., 1995) are present in the same glandular cells, random formation of dimeric precursors gives rise to both homodimers and heterodimers (Hekimi et al., 1991; Huybrechts et al., 2002). Further processing of L. migratoria APRPs from the AKH I and AKH II precursors takes place to yield additional peptides designated the adipokinetic hormone joining peptides (AKH-JP I and AKH-JP II), but their release was not demonstrated (Baggerman et al., 2002). Biological roles for the APRPs or the AKH-JPs have not been found (Oudejans et al., 1991; Hatle and Spring, 1999; Baggerman et al., 2002). Relative peptide levels in the glandular cells are controlled by multiple mechanisms. The 4.5:1 ratio of AKH I to AKH II present in the glandular cells (Hekimi et al., 1991) is regulated by a 1.7:1 ratio of AKH I to AKH II mRNA and the more efficient translation of AKH I mRNA (Fischer-Lougheed et al., 1993).Antisera specific to AKH I or AKH II have demonstrated their colocalization in the same secretory granules in the glandular cells of the CC (Diederen et al., 1987). Since an AKH III-specific antiserum is not available, the colocalization of each APRP implies that AKH III is also colocalized with AKH I and II (Harthoorn et al., 1999). The amount of AKHs increase dramatically in the CC during development (Siegert and Mordue, 1986b), due to their continued synthesis (Fischer-Lougheed et al., 1993; Oudejans et al., 1993) and to the increase in the number of cells in the glandular lobe of the CC (Kirschenbaum and O Shea, 1993). The continued synthesis of AKH generates a large pool of secretory granules in the glandular cells (Diederen et al., 1992), and newly synthesized AKH is preferentially released over AKHs stored in older secretory granules (Sharp-Baker et al., 1995), which constitutes a pool of peptides that cannot be released (Sharp-Baker et al., 1996; Harthoorn et al., 2002). Therefore, only a small percentage of the total AKH present in the glandular cells is released during flight (Cheeseman et al., 1976) or upon stimulation by CCAP (Harthoorn et al., 2002). The AKHs are released in the same proportion as their levels in the CC (Harthoorn et al., 1999), and the continuous synthesis of AKH is required for the secretion of peptides from the glandular cells in response to metabolic need (Harthoorn et al., 2002).In S. gregaria and L. migratoria, the hemolymph trehalose levels during flight are about 50% that of preflight values (Mayer and Candy, 1969b; Jutsum and Goldsworthy, 1976), and injection of a high concentration of trehalose prevents AKH release assayed by quantifying lipid mobilizing activity in the hemolymph (Cheeseman et al., 1976). Trehalose and glucose exert a direct action on the glandular cells of the CC, since high trehalose concentrations decreased both spontaneous AKH release and AKH release induced by the neuropeptide Locmi-TK I, 3-isobutyl-l-methylxanthine (IBMX), or high potassium concentrations in vitro (Passier et al., 1997). It was suggested that trehalose exerts this effect, in part, after its conversion to glucose. The decrease in trehalose concentration in response to the energy demands of flight relieves this inhibition, and is one of the factors that contributes to AKH release that is observed during flight (Cheeseman and Goldsworthy, 1979; Orchard and Lange, 1983b). It was also suggested that high levels of diacylglycerol resulting from mobilization of lipid energy stores may exert negative feedback on AKH release (Cheeseman and Goldsworthy, 1979).The neural and hormonal factors that modulate AKH release have been most thoroughly characterized in L. migratoria (Vullings et al., 1999). Implanted CC do not show the ultrastructural signs of enhanced AKH release during flight, suggesting that AKH secretion is under neural control by cells that make direct contact with the glandular lobe cells (Rademakers, 1977a). Neuroanatomical studies defined the secretomotor neurons in the lateral part of the protocerebrum that project through the nervi corporis cardiaci II (NCC II) to innervate the glandular lobe of the CC (GCC) and make synaptic contact with the AKH cells, and the axon terminals of the GCC are derived solely from the secretomotor cells (Rademakers, 1977b; Konings et al., 1989). Electrical stimulation of the NCC II resulted in the release of AKH I and II from the GCC and was accompanied by an increase in cAMP levels in cells of the GCC (Orchard and Loughton, 1981; Orchard and Lange, 1983a). While stimulation of the NCC I had no direct effect on AKH release, an enhancement of the NCC II-stimulated release of AKH from the CC was observed (Orchard and Loughton, 1981). Hormonally mediated lipid mobilization during flight is abolished in locusts in which the NCC I and NCC II were severed (Goldsworthy et al., 1972b). Together, these data indicate that the secretomotor neurons are involved in the control of AKH release, and compounds present in the NCC I modulate AKH secretion.An antiserum raised against locustatachykinin I (Locmi-TK I), a member of a family of structurally related neuropeptides (Schoofs et al., 1993), stained a subset of secretomotor neurons projecting to the GCC and made synaptoid contacts with AKH-immunoreactive glandular cells, suggesting a role for a Locmi-TK I-like peptide in AKH release (Nässel et al., 1995). Indeed, Locmi-TK I and II induced AKH release from the CC in vitro and increased cAMP levels in the GCC, but an effect on AKH release required concentrations in the 50–200 μM range (Nässel et al., 1995, 1999). Furthermore, four Locmi-TK isoforms were identified in L. migratoria CC extracts (Nässel et al., 1999). The anatomical features of the Locmi-TK-containing secretomotor neurons suggest that these peptides might act on synaptic receptors, and the high concentration of peptide required for AKH release is consistent with this hypothesis, particularly since synaptic receptors might be less accessible for an in vitro effect and thus would require higher peptide concentrations for an effect to be observed.SchistoFLRFamide is a member of a large family of neuropeptides known as the FMRFamide-related peptides (FaRPs) that are widely found in insects (Orchard et al., 2001). Antisera to FMRFamide and SchistoFLRFamide label a subset of secretomotor neurons that are distinct from the Locmi-TK-containing cells which make synaptoid contacts with glandular cells of the CC (Vullings et al., 1998). FMRFamide and SchistoFLRFamide have no effect on the spontaneous release of AKH in vitro, but reduced IBMX-induced AKH release at a 10 μM peptide concentration. Like the case with Locmi-TK neuropeptides, the high concentration of FaRPs required for an effect is consistent with a direct supply of peptides on the glandular cells. Thus, FaRPs are inhibitory neuromodulators that act to fine-tune the release of AKH to meet the energetic demands of the flying animal (Vullings et al., 1998).A direct approach was used to isolate a compound, the neuropeptide CCAP, from a S. gregaria brain extract that potently stimulates release of AKH from L. migratoria and S. gregaria CC in vitro (Veelaert et al., 1997). CCAP is a multifunctional neuropeptide and is best known for its stimulatory activity on heartbeat (Tublitz and Truman, 1985) and its effect as trigger for ecdysis behavior (Gammie and Truman, 1997; see Chapter 3.1). Unlike the Locmi-TK and SchistoFLRFamide-like peptides, there are no CCAP containing fibers in the GCC (Dircksen and Homberg, 1995; Veelaert et al., 1997); CCAP is active in the nM range indicating that it may act as a neurohormonal releasing factor for AKH (Veelaert et al., 1997).Flight activity increases the octopamine levels in the hemolymph of S. gregaria (Goosey and Candy, 1980), and in L. migratoria, octopamine was shown to stimulate AKH release from the CC in the presence of IBMX (Pannabecker and Orchard, 1986). It was later found that in this experimental design, octopamine potentiates the stimulatory effect of IBMX mediated cAMP elevation on AKH release, and has no effect on its own (Passier et al., 1995). This suggests that octopamine has a neurohormonal role in modulating AKH release (Veelaert et al., 1997).View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B044451924600034XAdipokinetic Hormones and Carbohydrate MetabolismWil J.A. Van Marrewijk, in Encyclopedia of Hormones, 2003III.C Inositol PhosphatesFor a maximal effect of AKH on glycogen phosphorylase activity in locust fat body, the release of Ca2+ from intracellular stores is required in addition to the availability of extracellular calcium. The same holds for the activation of glycogen phosphorylase and the stimulation of trehalose synthesis by HTH in B. discoidalis fat body. In the regulation of Ca2+ mobilization from intracellular stores, inositol phosphates (InsPn) play a pivotal role, and the formation of these putative second messengers is induced by the locust AKHs. Each of the Locusta AKHs stimulates the synthesis of total InsPn within 1 min with different potencies: AKH-II barely induces any InsPn and AKH-III is more potent than AKH-I. The observation that the activation of glycogen phosphorylase by each of the AKHs is dampened by the phospholipase C (PLC) inhibitor U73122 suggests the involvement of InsPn (and/or diacylglycerol) in AKH signaling in the locust fat body.All individual forms of InsPn are elevated by the AKHs, with InsP3 and InsP4 being the most interesting because of their presumed Ca2+ mobilizing actions (Fig. 3). With respect to InsP3, AKH-III is again more potent than AKH-I, and the AKH-II-enhanced InsP3 formation is quite small. The most prolonged effect on InsP3 is caused by AKH-III. The high potency and prolonged effects of AKH-III with respect to the induction of various second-messenger systems apparently compensate (in part) for its low abundance relative to that of the other AKHs, and therefore, the effects of this hormone may be stronger than estimated from its relative amount in the circulation.Figure 3. Effect of AKH on the formation of inositol phosphate isomers from locust fat body. Fat body tissue prelabeled with myo-[2-3H]inositol was incubated for 1 min in the presence or absence (controls) of 40 nM AKH-I; then InsPn were isolated and separated by high-performance liquid chromatography and their radioactivity was measured. Results are expressed as disintegrations per minute per milligram of protein.Ins(1,4,5)P3 levels are greatly increased by HTH in the fat body of B. discoidalis in a time- and dose-dependent manner, which, along with the strong evidence for Ca2+ as component in the HTH second-messenger cascade, argues strongly for InsP3 as a primary second messenger in response to HTH followed by the mobilization of intracellular Ca2+.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B012341103300005XFeeding-modulating neuropeptides and peptide hormones in insectsShinji Nagata, Yi Jun Zhou, in Advances in Insect Physiology, 20192.5.5 Fat body as an endocrine organInsulin and AKH are the two most significant endocrine factors to modulate some neuropeptide levels among all the peptides. Interestingly, insulin seems to be involved in a different system in addition to metabolic regulation as observed in the vertebrates. In most insect species, many insulin-like subtypes are present in a single species. For example, D. melanogaster has eight isoforms and B. mori has more than 40 isoforms. Interestingly, orthopteran species such as L. migratoria, S. gregaria and G. bimaculatus have only a single isoform. These isoforms are expressed extensively in the body, some are used for intraneuronal communications and some for systemic secretion in the hemolymph. The isoforms function differently according to the tissues expressing them. In most cases, transcriptional regulation seems to contribute to the distinctive insulin functions. Fat body is an organ to express and secrete the insulin isoforms for systemic signals.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/S0065280619300219Biochemistry and Molecular BiologyD.J. Van der Horst, R.O. Ryan, in Comprehensive Molecular Insect Science, 20054.6.2.3 Effect of Adipokinetic Hormones on Lipid MobilizationBinding of the AKHs to their plasma membrane receptor(s) at the fat body cells is the primary step to the induction of signal transduction events that ultimately lead to the activation of target key enzymes and the mobilization of lipids as a fuel for flight. Although the AKHs constitute extensively studied neurohormones and their actions have been shown to occur via G protein-coupled receptors (reviews: Van Marrewijk and Van der Horst, 1998; Vroemen et al., 1998), the general properties of which are remarkably well conserved during evolution (review: Vanden Broeck, 2001), the identification of these receptors has not been successful. Very recently, however, the first insect AKH receptors have been identified at the molecular level, namely those of the fruitfly Drosophila melanogaster and the silkworm Bombyx mori (Staubli et al., 2002). They appear to be structurally related to mammalian gonadotropin-releasing hormone (GnRH) receptors. These data promise to elucidate the nature of AKH receptors from other insects; it is envisaged that insects such as the locust, that produce two or more different types of AKH, may have two or more different AKH receptors.The signal transduction mechanism of the three locust AKHs has been studied extensively, and involves stimulation of cAMP production, which is dependent on the presence of extracellular Ca2+. Additionally, the AKHs enhance the production of inositol phosphates including inositol 1,4,5-trisphosphate (IP3), which may mediate the mobilization of Ca2+ from intracellular stores. This depletion of Ca2+ from intracellular stores stimulates the influx of extracellular Ca2+, indicative of the operation of a capacitative (store-operated) calcium entry mechanism. The interactions between the AKH signaling pathways ultimately result in mobilization of stored reserves as fuel for flight (reviews: Van Marrewijk and Van der Horst, 1998; Vroemen et al., 1998; Ryan and Van der Horst, 2000; Van der Horst et al., 2001; Van Marrewijk, 2003). The concentration of DAG in the hemolymph increases progressively at the expense of stored TAG reserves in the fat body, which implies hormonal activation of the key enzyme, fat body TAG lipase. In a bioassay, all three AKHs are able to stimulate lipid mobilization, although their relative potencies are different. This recalls the concept of a hormonally redundant system involving multiple regulatory molecules with overlapping actions (reviews: Goldsworthy et al., 1997; Vroemen et al., 1998). Results obtained with combinations of two or three AKHs, which are likely to occur together in locust hemolymph under physiological conditions in vivo, revealed that the maximal responses for the lipid-mobilizing effects were much lower than the theoretically calculated responses based on dose-response curves for the individual hormones. In the lower (probably physiological) range, however, combinations of the AKHs were more effective than the theoretical values calculated from the responses elicited by the individual hormones (review: Van Marrewijk and Van der Horst, 1998).The mechanism by which TAG lipase catalyzes AKH-controlled production of the DAG on which long-distance flight depends is only poorly understood, mainly due to technical problems in isolating or activating the lipase. In vertebrates, hormone-sensitive lipase (HSL) controls mobilization of TAG stores in adipose tissue, and although contrary to insects, free fatty acids (FFA) are released into the blood for uptake and oxidation in muscle, there is a clear functional similarity between vertebrate adipose tissue HSL and insect fat body TAG lipase (reviews: Ryan and Van der Horst, 2000; Van der Horst et al., 2001; Van der Horst and Oudejans, 2003).View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B0444519246000557Adipokinetic Hormones and Lipid Mobilization☆D.J. Van der Horst, R.C.H.M. Oudejans, in Reference Module in Neuroscience and Biobehavioral Psychology, 2017Adipokinetic Hormone Signal Transduction in Insect Fat BodyBinding of the peptide adipokinetic hormones to their G protein-coupled plasma membrane receptor(s) at the fat body cells results in the induction of a variety of signal transduction events that ultimately lead to the activation of target key enzymes. Following the identification of the first AKH receptors from the fruit fly Drosophila melanogaster and the silkworm Bombyx mori (Staubli et al., 2002) AKH receptors of several insect species have been identified at the molecular level; for the locust, however, the AKH receptor(s) are as yet unidentified (reviewed in Van der Horst and Ryan, 2012; Van der Horst and Rodenburg, 2012). The signal transduction mechanism of the three locust AKHs has been studied extensively and involves stimulation of cAMP production, which is dependent on the presence of extracellular Ca2+. Additionally, the AKHs enhance the production of inositol phosphates including inositol 1,4,5-trisphosphate, which may mediate the mobilization of Ca2+ from intracellular stores. This depletion of Ca2+ from intracellular stores stimulates the influx of extracellular Ca2+, indicative of the operation of a capacitative (store-operated) calcium entry mechanism (reviewed in Van Marrewijk and Van der Horst, 1998; Vroemen et al., 1998). The interactions between the AKH signaling pathways ultimately result in the mobilization of stored reserves as fuels for flight (for reviews, see Van der Horst et al., 2001; Van der Horst, 2003).Although the carbohydrate (mainly trehalose) in the insect blood (hemolymph) provides the energy for the initial period of flight, additional trehalose is mobilized from fat body glycogen reserves by the AKH-induced activation of glycogen phosphorylase. At the same time, the concentration of lipid (diacylglycerol, DAG) in the hemolymph is increased progressively at the expense of stored triacylglycerol (TAG) reserves in the fat body (Pines et al., 1981; Wang et al., 1990; Ziegler et al., 1990; Ryan and Van der Horst, 2000) and gradually constitutes the major substrate during prolonged flight.View chapterPurchase bookRead full chapterURL: https://www.sciencedirect.com/science/article/pii/B9780128093245033356Recommended publicationsInfo iconCurrent Opinion in Insect ScienceJournalAdvances in Insect PhysiologyBook seriesJournal of Insect PhysiologyJournalEncyclopedia of Insects (Second Edition)Book • 2009Browse books and journalsAbout ScienceDirectRemote accessShopping cartAdvertiseContact and supportTerms and conditionsPrivacy policyWe use cookies to help provide and enhance our service and tailor content and ads. By continuing you agree to the use of cookies.Copyright © 2021 Elsevier B.V. or its licensors or contributors. 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