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DINeR

A Database for Insect Neuropeptide Research

Search the database for information about the various species and neuropeptides of interest

Insect Neuropeptides - Adipokinetic Hormone

Introduction

Adipokinetic hormone (AKH) was one of the first insect peptides to be isolated, sequenced and synthesized. The first member of this peptide family was isolated from Locusta migratoria corpora cardiaca (Stone et al., 1976). AKH-related peptides have now been identified in numerous insects, and several other protostomes including arthropods, nematodes, annelids and mollusks (Gäde, 1997, Hauser and Grimmelikhuijzen, 2014; Li et al. 2016). With the exception of Caenorhabditis elegans AKH, all AKHs have an N-terminal pyroglutamate and a C-terminal amide (Hauser and Grimmelikhuijzen, 2014). Most amino acids of AKH are critical for receptor activation as determined by structure-activity relationships (Caers et al., 2012). The first AKH gene was cloned from Schistocerca gregaria (Schulz-Aellen et al., 1989). AKH precursors in insects also encode another peptide (AKH-Precursor Related Peptide; APRP), whose function is still unknown (Galikova et al., 2015). The first AKH receptors (GPCR) were deorphanized in Drosophila melanogaster and Bombyx mori (Park et al., 2002; Staubli et al., 2002). Arthropod AKH receptors are orthologous to the vertebrate GnRH receptors (Mirabeau and Joly, 2013). AKH is produced solely in the glandular cells of corpus cardiacum in studied insects. A few studies reported the presence of AKH-like material in brains of few insect species (Kaufmann and Brown, 2006; Kaufmann et al., 2009; Siegert, 1999). However, this can now be attributed to the recently discovered ACP neuropeptide which is structurally similar to AKH (Hansen et al., 2010).

Location

AKH is produced solely in the glandular cells of corpus cardiacum in studied insects. A few studies reported the presence of AKH-like material in brains of few insect species (Kaufmann and Brown, 2006; Kaufmann et al., 2009; Siegert, 1999). However, this can now be attributed to the recently discovered ACP neuropeptide which is structurally similar to AKH (Hansen et al., 2010).

Function

Since AKH was one of the first neuropeptides to identified quite a large number of publications are available that deal with its actions. In insects, AKH is primarily known for its role in mobilization of lipids, carbohydrates and proline from stores (such as the fat body) during flight/locomotion, reproduction, development and stress (Gäde et al., 1997; Gäde and Auerswald, 2003; Bharucha et al., 2008). In several species, it has also been reported to stimulate heart rate, inhibit protein and lipid synthesis, stimulate locomotor activity and stimulate myotropic contractions (Gäde et al., 1997; Gäde and Auerswald, 2003; Gäde 2009; Hauser and Grimmelikhuijzen, 2014; Nässel and Winther, 2010). In Drosophila, AKH has additionally been implicated in nutritional and oxidative stress responses and it extends lifespan under starvation conditions (Bednářová et al., 2015; Galikova et al., 2015; Sajwan et al., 2015; Waterson et al., 2014). Furthermore, AKH also regulates starvation-induced locomotor activity (Yu et al., 2016).

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Suggested Reviews

  • Gäde, G. (1997). The explosion of structural information on insect neuropeptides. Fortschr Chem Org Naturst 71, 1-128.
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  • Gäde, G., 2009. Peptides of the adipokinetic hormone/red pigment- concentrating hormone family: a new take on biodiversity. Ann. N. Y. Acad. Sci. 1163, 125–136.
    View Review
  • Gäde, G., and Auerswald, L. (2003). Mode of action of neuropeptides from the adipokinetic hormone family. Gen Comp Endocrinol 132, 10-20.
    View Review
  • Gäde, G., Hoffmann, K.H., and Spring, J.H. (1997). Hormonal regulation in insects: facts, gaps, and future directions. Physiol Rev 77, 963-1032.
    View Review
  • Hauser, F., Grimmelikhuijzen, C.J.P., 2014. Evolution of the AKH/corazonin/ACP/GnRH receptor superfamily and their ligands in the Protostomia. Gen. Comp. Endocrinol. 209, 35–49.
    View Review
  • Nässel, D.R., Winther, Å.M.E., 2010. Drosophila neuropeptides in regulation of physiology and behavior. Prog. Neurobiol. 92, 42–104.
    View Review

References

  • Bednářová, A., Kodrík, D., Krishnan, N., 2015. Knockdown of adipokinetic hormone synthesis increases susceptibility to oxidative stress in Drosophila - a role for dFoxO? Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 171, 8–14.
  • Bharucha, K.N., Tarr, P., and Zipursky, S.L. (2008). A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis. J Exp Biol 211, 3103-3110.
  • Caers, J., Peeters, L., Janssen, T., De Haes, W., Gäde, G., Schoofs, L., 2012. Structure-activity studies of Drosophila adipokinetic hormone (AKH) by a cellular expression system of dipteran AKH receptors. Gen. Comp. Endocrinol. 177, 332–337.
  • Galikova, M., Diesner, M., Klepsatel, P., Hehlert, P., Xu, Y., Bickmeyer, I., Predel, R., and Kuhnlein, R.P. (2015). Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants. Genetics 201, 665-683.
  • Hansen, K.K., Stafflinger, E., Schneider, M., Hauser, F., Cazzamali, G., Williamson, M., Kollmann, M., Schachtner, J., Grimmelikhuijzen, C.J.P., 2010. Discovery of a novel insect neuropeptide signaling system closely related to the insect adipokinetic hormone and corazonin hormonal systems. J. Biol. Chem. 285, 10736–10747.
  • Kaufmann, C., Brown, M.R., 2006. Adipokinetic hormones in the African malaria mosquito, Anopheles gambiae: Identification and expression of genes for two peptides and a putative receptor. Insect Biochem. Mol. Biol. 36, 466–481.
  • Kaufmann, C., Merzendorfer, H., Gäde, G., 2009. The adipokinetic hormone system in Culicinae (Diptera: Culicidae): Molecular identification and characterization of two adipokinetic hormone (AKH) precursors from Aedes aegypti and Culex pipiens and two putative AKH receptor variants from A. aegypti. Insect Biochem. Mol. Biol. 39, 770–781.
  • Li S, Hauser F, Skadborg SK, Nielsen SV, Kirketerp-Møller N, Grimmelikhuijzen CJ., 2016. Adipokinetic hormones and their G protein-coupled receptors emerged in Lophotrochozoa. Sci. Rep. 6, 32789; doi: 10.1038/srep32789 (2016).
  • Mirabeau, O., Joly, J.-S., 2013. Molecular evolution of peptidergic signaling systems in bilaterians. Proc. Natl. Acad. Sci. U. S. A. 110, E2028–37.
  • Park, Y., Kim, Y.-J., Adams, M.E., 2002. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution. Proc. Natl. Acad. Sci. U. S. A. 99, 11423–11428.
  • Sajwan, S., Sidorov, R., Stašková, T., Žaloudíková, A., Takasu, Y., Kodrík, D., Zurovec, M., 2015. Targeted mutagenesis and functional analysis of adipokinetic hormone-encoding gene in Drosophila. Insect Biochem. Mol. Biol. 61, 79–86.
  • Schulz-Aellen, M.-F., Roulet, E., Fischer-Lougheed, J., O’Shea, M., 1989. A synthesis of a homodimer neurohormone precursor of locust adipokinetic hormone studied by in vitro translation and cDNA cloning. Neuron 2, 1369–1373.
  • Siegert, K.J., 1999. Locust corpora cardiaca contain an inactive adipokinetic hormone. FEBS Lett. 447, 237–240.
  • Staubli, F., Jorgensen, T.J.D., Cazzamali, G., Williamson, M., Lenz, C., Sondergaard, L., Roepstorff, P., Grimmelikhuijzen, C.J.P., 2002. Molecular identification of the insect adipokinetic hormone receptors. Proc. Natl. Acad. Sci. U. S. A. 99, 3446–3451.
  • Stone, J. V., Mordue, W., Batley, K.E., Morris, H.R., 1976. Structure of locust adipokinetic hormone, a neurohormone that regulates lipid utilisation during flight. Nature 263, 207–211.
  • Waterson, M.J., Chung, B.Y., Harvanek, Z.M., Ostojic, I., Alcedo, J., Pletcher, S.D., 2014. Water sensor ppk28 modulates Drosophila lifespan and physiology through AKH signaling. Proc. Natl. Acad. Sci. U. S. A. 111, 8137–42.
  • Yu Y, Huang R, Ye J, Zhang V, Wu C, Cheng G, Jia J, Wang L. 2016. Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila. eLife 2016;5:e15693. DOI: 10.7554/eLife.15693