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Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells

Nature volume 431, pages 316–320 (2004)Cite this article

Abstract

Antagonistic activities of glucagon and insulin control metabolism in mammals, and disruption of this balance underlies diabetes pathogenesis. Insulin-producing cells (IPCs) in the brain of insects such as Drosophila also regulate serum glucose1,2, but it remains unclear whether insulin is the sole hormonal regulator of glucose homeostasis and whether mechanisms of glucose-sensing and response in IPCs resemble those in pancreatic islets. Here we show, by targeted cell ablation, that Drosophila corpora cardiaca (CC) cells3,4,5 of the ring gland are also essential for larval glucose homeostasis. Unlike IPCs, CC cells express Drosophila cognates of sulphonylurea receptor (Sur) and potassium channel (Ir), proteins that comprise ATP-sensitive potassium channels regulating hormone secretion by islets and other mammalian glucose-sensing cells6,7,8. They also produce adipokinetic hormone, a polypeptide with glucagon-like functions. Glucose regulation by CC cells is impaired by exposure to sulphonylureas, drugs that target the Sur subunit. Furthermore, ubiquitous expression of an akh transgene reverses the effect of CC ablation on serum glucose. Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells.

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Figure 1: Haemolymph glucose regulation by KATP channel-expressing cells in the corpora cardiaca.
Figure 2: akh gene expression and morphology of akh-expressing cells.
Figure 3: Changes in fluorescence intensity in akh-expressing cells producing camgaroo-2 (cg-2).

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Acknowledgements

We thank B. Tsai for Ir and Sur cloning and in situ hybridizations, X. Gu for akh cloning and constructions, G. McLean for fly husbandry, E. Bustamante for glucose assays, M. Fish for P-element-mediated transformations, P. Calvert for quantitative analysis of calcium transients, and R. Nusse, G. Barsh, M. Krasnow, S. DiNardo and members of the Rulifson and Kim laboratories for suggestions on the manuscript. E.R. was supported by a grant from the Juvenile Diabetes Research Foundation (JDRF). S.K. was supported by grants from the JDRF, the Pew Charitable Trusts and the Verto Institute. E.R. and S.K. contributed equally to this study.

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  1. Departments of Developmental Biology and Medicine (Oncology Division), Stanford University School of Medicine, Beckman Center B300, Stanford, California, 94305-5329, USA

    Seung K. Kim

  2. Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 1214 BRB II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania, 19104-6058, USA

    Eric J. Rulifson

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Correspondence to Seung K. Kim.

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Kim, S., Rulifson, E. Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature 431, 316–320 (2004). https://doi.org/10.1038/nature02897

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