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Genetics. 2004 May; 167(1): 311–323.
PMCID: PMC1470856

Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila melanogaster.


Adipokinetic hormones (AKHs) are metabolic neuropeptides, mediating mobilization of energy substrates from the fat body in many insects. In delving into the roles of the Drosophila Akh (dAkh) gene, its developmental expression patterns were examined and the physiological functions of the AKH-producing neurons were investigated using animals devoid of AKH neurons and ones with ectopically expressing dAkh. The dAkh gene is expressed exclusively in the corpora cardiaca from late embryos to adult stages. Projections emanating from the AKH neurons indicated that AKH has multiple target tissues as follows: the prothoracic gland and aorta in the larva and the crop and brain in the adult. Studies using transgenic manipulations of the dAkh gene demonstrated that AKH induced both hypertrehalosemia and hyperlipemia. Starved wild-type flies displayed prolonged hyperactivity prior to death; this novel behavioral pattern could be associated with food-searching activities in response to starvation. In contrast, flies devoid of AKH neurons not only lacked this type of hyperactivity, but also displayed strong resistance to starvation-induced death. From these findings, we propose another role for AKH in the regulation of starvation-induced foraging behavior.

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Selected References

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  • Aggarwal SK, King RC. An electron microscopic study of the corpus cardiacum of adult Drosophila melanogaster and its afferent nerves. J Morphol. 1971 Aug;134(4):437–445. [PubMed]
  • An W, Wensink PC. Integrating sex- and tissue-specific regulation within a single Drosophila enhancer. Genes Dev. 1995 Jan 15;9(2):256–266. [PubMed]
  • Arrese EL, Wells MA. Adipokinetic hormone-induced lipolysis in the fat body of an insect, Manduca sexta: synthesis of sn-1,2-diacylglycerols. J Lipid Res. 1997 Jan;38(1):68–76. [PubMed]
  • Konopka RJ, Hamblen-Coyle MJ, Jamison CF, Hall JC. An ultrashort clock mutation at the period locus of Drosophila melanogaster that reveals some new features of the fly's circadian system. J Biol Rhythms. 1994 Winter;9(3-4):189–216. [PubMed]
  • Lee G, Foss M, Goodwin SF, Carlo T, Taylor BJ, Hall JC. Spatial, temporal, and sexually dimorphic expression patterns of the fruitless gene in the Drosophila central nervous system. J Neurobiol. 2000 Jun 15;43(4):404–426. [PubMed]
  • Lee T, Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999 Mar;22(3):451–461. [PubMed]
  • Bradfield JY, Lee YH, Keeley LL. Cytochrome P450 family 4 in a cockroach: molecular cloning and regulation by regulation by hypertrehalosemic hormone. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4558–4562. [PMC free article] [PubMed]
  • Lorenz MW, Kellner R, Völkl W, Hoffmann KH, Woodring J. A comparative study on hypertrehalosaemic hormones in the Hymenoptera: sequence determination, physiological actions and biological significance. J Insect Physiol. 2001 Jun;47(6):563–571. [PubMed]
  • Bradley RL, Cleveland KA, Cheatham B. The adipocyte as a secretory organ: mechanisms of vesicle transport and secretory pathways. Recent Prog Horm Res. 2001;56:329–358. [PubMed]
  • Britton JS, Edgar BA. Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development. 1998 Jun;125(11):2149–2158. [PubMed]
  • Lorenz MW, Kellner R, Woodring J, Hoffmann KH, Gäde G. Hypertrehalosaemic peptides in the honeybee (Apis mellifera): purification, identification and function. J Insect Physiol. 1999 Jul;45(7):647–653. [PubMed]
  • Britton Jessica S, Lockwood Wendy K, Li Ling, Cohen Stephen M, Edgar Bruce A. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell. 2002 Feb;2(2):239–249. [PubMed]
  • Mattson Mark P. Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism. Mech Ageing Dev. 2002 Apr 30;123(8):947–953. [PubMed]
  • Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R, Hafen E. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr Biol. 2001 Feb 20;11(4):213–221. [PubMed]
  • McNabb SL, Baker JD, Agapite J, Steller H, Riddiford LM, Truman JW. Disruption of a behavioral sequence by targeted death of peptidergic neurons in Drosophila. Neuron. 1997 Oct;19(4):813–823. [PubMed]
  • Milde JJ, Ziegler R, Wallstein M. Adipokinetic hormone stimulates neurones in the insect central nervous system. J Exp Biol. 1995 Jun;198(Pt 6):1307–1311. [PubMed]
  • Noyes BE, Katz FN, Schaffer MH. Identification and expression of the Drosophila adipokinetic hormone gene. Mol Cell Endocrinol. 1995 Apr 1;109(2):133–141. [PubMed]
  • Chino H, Kiyomoto Y, Takahashi K. In vitro study of the action of adipokinetic hormone in locusts. J Lipid Res. 1989 Apr;30(4):571–578. [PubMed]
  • Park Jae H. Downloading central clock information in Drosophila. Mol Neurobiol. 2002 Oct-Dec;26(2-3):217–233. [PubMed]
  • Dai JD, Gilbert LI. Metamorphosis of the corpus allatum and degeneration of the prothoracic glands during the larval-pupal-adult transformation of Drosophila melanogaster: a cytophysiological analysis of the ring gland. Dev Biol. 1991 Apr;144(2):309–326. [PubMed]
  • Park JH, Hall JC. Isolation and chronobiological analysis of a neuropeptide pigment-dispersing factor gene in Drosophila melanogaster. J Biol Rhythms. 1998 Jun;13(3):219–228. [PubMed]
  • Park JH, Keeley LL. In vitro hormonal regulation of glycogen phosphorylase activity in fat body of the tropical cockroach, Blaberus discoidalis. Gen Comp Endocrinol. 1995 Jun;98(3):234–243. [PubMed]
  • Diederen Jacques H B, Oudejans Rob C H M, Harthoorn Lucien F, Van der Horst Dick J. Cell biology of the adipokinetic hormone-producing neurosecretory cells in the locust corpus cardiacum. Microsc Res Tech. 2002 Feb 1;56(3):227–236. [PubMed]
  • Dimitriadis VK, Papamanoli E. Functional morphology of the crop of Drosophila auraria. Cytobios. 1992;69(278-279):143–152. [PubMed]
  • Gäde G, Wilps H, Kellner R. Isolation and structure of a novel charged member of the red-pigment-concentrating hormone-adipokinetic hormone family of peptides isolated from the corpora cardiaca of the blowfly Phormia terraenovae (Diptera). Biochem J. 1990 Jul 15;269(2):309–313. [PMC free article] [PubMed]
  • Park Jae H, Schroeder Andrew J, Helfrich-Förster Charlotte, Jackson F Rob, Ewer John. Targeted ablation of CCAP neuropeptide-containing neurons of Drosophila causes specific defects in execution and circadian timing of ecdysis behavior. Development. 2003 Jun;130(12):2645–2656. [PubMed]
  • Gäde G, Hoffmann KH, Spring JH. Hormonal regulation in insects: facts, gaps, and future directions. Physiol Rev. 1997 Oct;77(4):963–1032. [PubMed]
  • Phelps CB, Brand AH. Ectopic gene expression in Drosophila using GAL4 system. Methods. 1998 Apr;14(4):367–379. [PubMed]
  • Garfias A, RodrÍGuez-Sosa L, ArÉChiga H. Modulation of crayfish retinal function by red pigment concentrating hormone. J Exp Biol. 1995;198(Pt 7):1447–1454. [PubMed]
  • Porras MG, López-Colomé AM, Aréchiga H. Red pigment-concentrating hormone induces a calcium-mediated retraction of distal retinal pigments in the crayfish. J Comp Physiol A. 2001 Jun;187(5):349–357. [PubMed]
  • Hall Jeffrey C. Genetics and molecular biology of rhythms in Drosophila and other insects. Adv Genet. 2003;48:1–280. [PubMed]
  • Harthoorn LF, Oudejans RC, Diederen JH, Van de Wijngaart DJ, Van der Horst DJ. Absence of coupling between release and biosynthesis of peptide hormones in insect neuroendocrine cells. Eur J Cell Biol. 2001 Jul;80(7):451–457. [PubMed]
  • Renn SC, Park JH, Rosbash M, Hall JC, Taghert PH. A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila. Cell. 1999 Dec 23;99(7):791–802. [PubMed]
  • Hay BA, Wolff T, Rubin GM. Expression of baculovirus P35 prevents cell death in Drosophila. Development. 1994 Aug;120(8):2121–2129. [PubMed]
  • Helfrich-Förster C, Täuber M, Park JH, Mühlig-Versen M, Schneuwly S, Hofbauer A. Ectopic expression of the neuropeptide pigment-dispersing factor alters behavioral rhythms in Drosophila melanogaster. J Neurosci. 2000 May 1;20(9):3339–3353. [PubMed]
  • Rulifson Eric J, Kim Seung K, Nusse Roel. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science. 2002 May 10;296(5570):1118–1120. [PubMed]
  • Jaffe H, Raina AK, Riley CT, Fraser BA, Nachman RJ, Vogel VW, Zhang YS, Hayes DK. Primary structure of two neuropeptide hormones with adipokinetic and hypotrehalosemic activity isolated from the corpora cardiaca of horse flies (Diptera). Proc Natl Acad Sci U S A. 1989 Oct;86(20):8161–8164. [PMC free article] [PubMed]
  • Satake S, Masumura M, Ishizaki H, Nagata K, Kataoka H, Suzuki A, Mizoguchi A. Bombyxin, an insulin-related peptide of insects, reduces the major storage carbohydrates in the silkworm Bombyx mori. Comp Biochem Physiol B Biochem Mol Biol. 1997 Oct;118(2):349–357. [PubMed]
  • Schaffer MH, Noyes BE, Slaughter CA, Thorne GC, Gaskell SJ. The fruitfly Drosophila melanogaster contains a novel charged adipokinetic-hormone-family peptide. Biochem J. 1990 Jul 15;269(2):315–320. [PMC free article] [PubMed]
  • Sharma Yashoda, Cheung Una, Larsen Ellen W, Eberl Daniel F. PPTGAL, a convenient Gal4 P-element vector for testing expression of enhancer fragments in drosophila. Genesis. 2002 Sep-Oct;34(1-2):115–118. [PMC free article] [PubMed]
  • Veelaert D, Schoofs L, De Loof A. Peptidergic control of the corpus cardiacum-corpora allata complex of locusts. Int Rev Cytol. 1998;182:249–302. [PubMed]
  • White K, Tahaoglu E, Steller H. Cell killing by the Drosophila gene reaper. Science. 1996 Feb 9;271(5250):805–807. [PubMed]
  • Stone JV, Mordue W, Batley KE, Morris HR. Structure of locust adipokinetic hormone, a neurohormone that regulates lipid utilisation during flight. Nature. 1976 Sep 16;263(5574):207–211. [PubMed]
  • Ziegler R, Eckart K, Law JH. Adipokinetic hormone controls lipid metabolism in adults and carbohydrate metabolism in larvae of Manduca sexta. Peptides. 1990 Sep-Oct;11(5):1037–1040. [PubMed]
  • Zinke I, Kirchner C, Chao LC, Tetzlaff MT, Pankratz MJ. Suppression of food intake and growth by amino acids in Drosophila: the role of pumpless, a fat body expressed gene with homology to vertebrate glycine cleavage system. Development. 1999 Dec;126(23):5275–5284. [PubMed]
  • Van der Horst DJ, Van Marrewijk WJ, Diederen JH. Adipokinetic hormones of insect: release, signal transduction, and responses. Int Rev Cytol. 2001;211:179–240. [PubMed]

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