Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells.
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 glucose, 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) cells 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 cells. 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.
Kim
Seung K
SK
Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B300, Stanford, California 94305-5329, USA. seungkim@cmgm.stanford.edu
Rulifson
Eric J
EJ
D018528:ATP-Binding Cassette Transporters / Q000819:agonists / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004702:Endocrine Glands / Q000166:cytology* / Q000502:physiology*; D017344:Genes, Insect / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006458:Hemolymph / Q000378:metabolism; D006706:Homeostasis; D007301:Insect Hormones / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011955:Receptors, Drug / Q000819:agonists / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D064233:Sulfonylurea Receptors; D019076:Transgenes / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D029721:Drosophila Proteins; D007301:Insect Hormones; D009842:Oligopeptides; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; C044833:adipokinetic hormone; C577513:sulfonylurea receptor, Drosophila; D005947:Glucose; D011761:Pyrrolidonecarboxylic Acid