A glucose-sensing neuron pair regulates insulin and glucagon in Drosophila

Although glucose-sensing neurons were identified more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here we identify a pair of glucose-sensing neurons with bifurcated axons in the brain of Drosophila. One axon branch projects to insulin-producing cells to...

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Published inNature (London) Vol. 574; no. 7779; pp. 559 - 564
Main Authors Oh, Yangkyun, Lai, Jason Sih-Yu, Mills, Holly J, Erdjument-Bromage, Hediye, Giammarinaro, Benno, Saadipour, Khalil, Wang, Justin G, Abu, Farhan, Neubert, Thomas A, Suh, Greg S B
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.10.2019
Subjects
Animals
Axons
Axons - metabolism
Bifurcations
Biological control systems
Brain - anatomy & histology
Brain - metabolism
Chemoreception
Corpora cardiaca
Detection
Diabetes
Diabetes mellitus
Drosophila
Drosophila melanogaster - anatomy & histology
Drosophila melanogaster - cytology
Drosophila melanogaster - metabolism
Drosophila Proteins - metabolism
Energy balance
Glucagon
Glucagon - metabolism
Glucose
Glucose - analysis
Glucose - metabolism
Hemolymph
Homeostasis
Hyperglycemia
Insect Hormones - metabolism
Insects
Insulin
Insulin - metabolism
Internal energy
Male
Menopause
Neural Inhibition
Neural Pathways
Neurons
Neurons - metabolism
Neuropeptides
Neuropeptides - chemistry
Neuropeptides - metabolism
Neurotransmitter Agents - metabolism
Observations
Oligopeptides - metabolism
Peptides
Physiological aspects
Physiology
Proteomics
Pyrrolidonecarboxylic Acid - analogs & derivatives
Pyrrolidonecarboxylic Acid - metabolism
Secretion
United States
United States > US
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Summary:Although glucose-sensing neurons were identified more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here we identify a pair of glucose-sensing neurons with bifurcated axons in the brain of Drosophila. One axon branch projects to insulin-producing cells to trigger the release of Drosophila insulin-like peptide 2 (dilp2) and the other extends to adipokinetic hormone (AKH)-producing cells to inhibit secretion of AKH, the fly analogue of glucagon. These axonal branches undergo synaptic remodelling in response to changes in their internal energy status. Silencing of these glucose-sensing neurons largely disabled the response of insulin-producing cells to glucose and dilp2 secretion, disinhibited AKH secretion in corpora cardiaca and caused hyperglycaemia, a hallmark feature of diabetes mellitus. We propose that these glucose-sensing neurons maintain glucose homeostasis by promoting the secretion of dilp2 and suppressing the release of AKH when haemolymph glucose levels are high.
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Y.O. performed nearly all immunohistochemistry, calcium imaging, behavior testing, hemolymph glycemia measurement, statistical analyses, and figure design. J.S.L., H.J.M., and B.G. carried out a Gal4 screen using the two-choice assay. H.E.B and T.A.N conducted mass spectrometry to measure the dilp2 and AKH levels in hemolymph. K.S performed dot blot assay to measure the dilp2 and AKH levels in hemolymph. J.G.W. performed feeding assay and assisted in measuring hemolymph glycemia. F.A. assisted CaLexA experiment. G.S.B.S. supervised the project and provided intellectual support. Y.O. and G.S.B.S. wrote the manuscript with inputs from other authors.
Present addresses: QPS-Qualitix Taiwan, Ren-Ai Road, Taipei, Taiwan (J.S.L.); Ascend Public Charter Schools, New York, NY, USA. (H.J.m); Vision Sciences Graduate Program, School of Optometry, UC Berkeley, Berkeley, CA, USA (B.G.); Salk Institute for Biological Studies, La Jolla, CA, USA (J.G.W.); Department of Genetics and Development, Columbia University, New York, NY, UAS. (f.A.)
Author contributions
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-019-1675-4