Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity in Drosophila.

Insulin signaling pathways are implicated in several physiological processes in invertebrates, including the control of growth and life span; the latter of these has also been correlated with juvenile hormone (JH) deficiency. In turn, JH levels have been correlated with sex-specific differences in locomotor activity. Here, the involvement of the insulin signaling pathway in sex-specific differences in locomotor activity was investigated in Drosophila. Ablation of insulin-producing neurons in the adult pars-intercerebralis was found to increase trehalosemia and to abolish sexual dimorphism relevant to locomotion. Conversely, hyper-insulinemia induced by insulin injection or by over-expression of an insulin-like peptide decreases trehalosemia but does not affect locomotive behavior. Moreover, we also show that in the head of adult flies, the insulin receptor (InR) is expressed only in the fat body surrounding the brain. While both male and female InR mutants are hyper-trehalosemic, they exhibit similar patterns of locomotor activity. Our results indicate that first, insulin controls trehalosemia in adults, and second, like JH, it controls sex-specific differences in the locomotor activity of adult Drosophila in a manner independent of its effect on trehalose metabolism.

[1]  M. Heisenberg,et al.  Isolation of Anatomical Brain Mutants of Drosophila by Histological Means , 1979 .

[2]  E. Balaban,et al.  The Differences between the Sexes , 1994 .

[3]  O. Rosen,et al.  Tissue localization of Drosophila melanogaster insulin receptor transcripts during development , 1988, Molecular and cellular biology.

[4]  K. Nairz,et al.  Nutrient-Dependent Expression of Insulin-like Peptides from Neuroendocrine Cells in the CNS Contributes to Growth Regulation in Drosophila , 2002, Current Biology.

[5]  A. Mizoguchi,et al.  Glucose stimulates the release of bombyxin, an insulin-related peptide of the silkworm Bombyx mori. , 2000, General and comparative endocrinology.

[6]  M. Tatar,et al.  A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function , 2001, Science.

[7]  E. Rulifson,et al.  Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells , 2004, Nature.

[8]  E. Hafen,et al.  Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein , 2001, Science.

[9]  Jean-René Martin,et al.  AKH-producing neuroendocrine cell ablation decreases trehalose and induces behavioral changes in Drosophila. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[10]  E. Hafen,et al.  Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Shilo,et al.  Interallelic complementation among DER/flb alleles: implications for the mechanism of signal transduction by receptor-tyrosine kinases. , 1991, Genetics.

[12]  Jean-René Martin A portrait of locomotor behaviour in Drosophila determined by a video-tracking paradigm , 2004, Behavioural Processes.

[13]  Jean-René Martin,et al.  Genetic identification of neurons controlling a sexually dimorphic behaviour , 2000, Current Biology.

[14]  E. Hafen,et al.  An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control , 2001, Current Biology.

[15]  H. Amrein,et al.  Genes expressed in the Drosophila head reveal a role for fat cells in sex‐specific physiology , 2002, The EMBO journal.

[16]  Mark R. Brown,et al.  Localization of an insulin-like peptide in brains of two flies , 2001, Cell and Tissue Research.

[17]  M. Frasch,et al.  The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. , 1995, The EMBO journal.

[18]  M. Heisenberg,et al.  Temporal pattern of locomotor activity in Drosophila melanogaster , 1999, Journal of Comparative Physiology A.

[19]  K. R. Weiss,et al.  Insulin Prohormone Processing, Distribution, and Relation to Metabolism in Aplysia californica , 1999, The Journal of Neuroscience.

[20]  B. Dauwalder,et al.  The Drosophila takeout gene is regulated by the somatic sex-determination pathway and affects male courtship behavior. , 2002, Genes & development.

[21]  Ronald L. Davis,et al.  Spatiotemporal Gene Expression Targeting with the TARGET and Gene-Switch Systems in Drosophila , 2004, Science's STKE.

[22]  V. Wigglesworth,et al.  The utilization of reserve substances in Drosophila during flight. , 1949, The Journal of experimental biology.

[23]  K. Behar,et al.  Role of Trehalose Phosphate Synthase in Anoxia Tolerance and Development in Drosophila melanogaster * , 2002, The Journal of Biological Chemistry.

[24]  G. Gäde,et al.  Hormonal regulation in insects: facts, gaps, and future directions. , 1997, Physiological reviews.

[25]  F. Foufelle,et al.  New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. , 2002, The Biochemical journal.

[26]  K. Nagata,et al.  Bombyxin, an insulin-related peptide of insects, reduces the major storage carbohydrates in the silkworm Bombyx mori. , 1997, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[27]  R. Nusse,et al.  Ablation of Insulin-Producing Neurons in Flies: Growth and Diabetic Phenotypes , 2002, Science.

[28]  G. Ness,et al.  Identification of insulin-responsive regions in the HMG-CoA reductase promoter. , 2004, Biochemical and biophysical research communications.

[29]  J. S. Britton,et al.  Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. , 2002, Developmental cell.

[30]  V. Budnik,et al.  Insulin-like receptor and insulin-like peptide are localized at neuromuscular junctions in Drosophila , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  James W Truman,et al.  Disruption of a Behavioral Sequence by Targeted Death of Peptidergic Neurons in Drosophila , 1997, Neuron.

[32]  Jean-René Martin,et al.  Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[33]  T. Normann Neurosecretory cells in insect brain and production of hypoglycaemic hormone , 1975, Nature.

[34]  F. Couillaud,et al.  The HMG-CoA reductase inhibitor fluvastatin inhibits insect juvenile hormone biosynthesis. , 1994, General and comparative endocrinology.

[35]  JF Ferveur,et al.  Genetic feminization of brain structures and changed sexual orientation in male Drosophila , 1995, Science.

[36]  W. Geraerts,et al.  Evolutionary conservation of the insulin gene structure in invertebrates: cloning of the gene encoding molluscan insulin-related peptide III from Lymnaea stagnalis. , 1993, Journal of molecular endocrinology.

[37]  R. Garofalo,et al.  The Drosophila insulin receptor is required for normal growth. , 1996, Endocrinology.

[38]  Gyunghee Lee,et al.  Hemolymph Sugar Homeostasis and Starvation-Induced Hyperactivity Affected by Genetic Manipulations of the Adipokinetic Hormone-Encoding Gene in Drosophila melanogaster , 2004, Genetics.