{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:44:32Z","timestamp":1792572272611,"version":"4.5.0"},"reference-count":16,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5570","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2002,5,10]]},"abstract":"<jats:p>\n                    In the fruit fly\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , four insulin genes are coexpressed in small clusters of cells [insulin-producing cells (IPCs)] in the brain. Here, we show that ablation of these IPCs causes developmental delay, growth retardation, and elevated carbohydrate levels in larval hemolymph. All of the defects were reversed by ectopic expression of a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    insulin transgene. On the basis of these functional data and the observation that IPCs release insulin into the circulatory system, we conclude that brain IPCs are the main systemic supply of insulin during larval growth. We propose that IPCs and pancreatic islet \u03b2 cells are functionally analogous and may have evolved from a common ancestral insulin-producing neuron. Interestingly, the phenotype of flies lacking IPCs includes certain features of diabetes mellitus.\n                  <\/jats:p>","DOI":"10.1126\/science.1070058","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:54:32Z","timestamp":1027749272000},"page":"1118-1120","source":"Crossref","is-referenced-by-count":982,"title":["Ablation of Insulin-Producing Neurons in Flies: Growth and Diabetic Phenotypes"],"prefix":"10.1126","volume":"296","author":[{"given":"Eric J.","family":"Rulifson","sequence":"first","affiliation":[{"name":"Department of Developmental Biology,"},{"name":"Howard Hughes Medical Institute, Beckman Center B300, Stanford University, Stanford, CA 94305\u20135329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology,"},{"name":"Department of Medicine (Oncology Division),"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Nusse","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology,"},{"name":"Howard Hughes Medical Institute, Beckman Center B300, Stanford University, Stanford, CA 94305\u20135329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","unstructured":"W. Brogiolo et al. Curr. Biol. 11 213 (2001).","DOI":"10.1016\/S0960-9822(01)00068-9"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","unstructured":"S. L. McNabb et al. Neuron 19 813 (1997).","DOI":"10.1016\/S0896-6273(00)80963-0"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.3.8603594"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","unstructured":"R. Bohni et al. Cell 97 865 (1999).","DOI":"10.1016\/S0092-8674(00)80799-0"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1146\/annurev.en.06.010161.000451","volume":"6","author":"Wyatt G. R.","year":"1961","unstructured":"Wyatt G. R., Annu. Rev. Entomol. 6, 75 (1961).","journal-title":"Annu. Rev. Entomol."},{"key":"e_1_3_1_7_2","unstructured":"B. Duvillie et al. Proc. Natl. Acad. Sci. U.S.A. 94 5137 (1997)."},{"key":"e_1_3_1_8_2","unstructured":"E. P. Joslin C. R. Kahn G. C. Weir Joslin's Diabetes Mellitus (Lea & Febiger Philadelphia PA ed. 13 1994)."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0303-7207(95)03492-P","volume":"109","author":"Noyes B. E.","year":"1995","unstructured":"Noyes B. E., Katz F. N., Schaffer M. H., Mol. Cell. Endocrinol. 109, 133 (1995).","journal-title":"Mol. Cell. Endocrinol."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","unstructured":"H. F. Nijhout Insect Hormones (Princeton Univ. Press Princeton NJ 1994).","DOI":"10.1515\/9780691225111"},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0303-7207(98)00079-3","volume":"141","author":"Vroemen S. F.","year":"1998","unstructured":"Vroemen S. F., Van der Horst D. J., Van Marrewijk W. J., Mol. Cell. Endocrinol. 141, 7 (1998).","journal-title":"Mol. Cell. 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W.","year":"1986","unstructured":"Clarke D. W., Mudd L., Boyd F. T., Fields M., Raizada M. K., J. Neurochem. 47, 831 (1986).","journal-title":"J. Neurochem."},{"key":"e_1_3_1_17_2","unstructured":"We thank K. Willert for help in antibody production J. Peterson for help with in situ hybridization and M. Fish for help with P element transformation. Supported by the Juvenile Diabetes Research Foundation (E.J.R.) and the Pew Charitable Trusts (S.K.K.). Supporting Online Material (www.sciencemag.org\/cgi\/content\/full\/296\/5570\/1118\/DC1) Materials and Methods figs. S1 to S6"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1070058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:34:33Z","timestamp":1704836073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1070058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,10]]},"references-count":16,"journal-issue":{"issue":"5570","published-print":{"date-parts":[[2002,5,10]]}},"alternative-id":["10.1126\/science.1070058"],"URL":"https:\/\/doi.org\/10.1126\/science.1070058","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1006234.78105","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,10]]}}}