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

Yangkyun Oh, Jason Sih Yu Lai, Holly J. Mills, Hediye Erdjument-Bromage, Benno Giammarinaro, Khalil Saadipour, Justin G. Wang, Farhan Abu, Thomas A. Neubert, Greg S.B. Suh

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalNature
Volume574
Issue number7779
DOIs
StatePublished - 24 Oct 2019

Bibliographical note

Funding Information:
Acknowledgements We thank M. Kanai and J.-Y. Park for providing expertise on the two-choice behaviour assay and physiology. We also thank S. K. Kim, J. Veenstra, J. H. Park and E. Hafen for providing antibodies used in this study; B. Levin, G. Schwartz, J. W. Sohn, H. Kim and the Suh laboratory members for stimulating discussion. This work is supported by NIH R01 grants (R01DK116294, R01DK106636 to G.S.B.S. and NINDS P30NS050276 to T.A.N.), KAIST Chancellor’s fund and a grant from Samsung Science & Technology Foundation (G.S.B.S).

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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