Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 46; pp. 19617 - 19622
• Main Authors: Zhang, Hua, Liu, Jingnan, Li, Caroline R, Momen, Bahram, Kohanski, Ronald A, Pick, Leslie
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 17.11.2009; National Acad Sciences
• Subjects: animal disease models; Animals; Autophagy; Biological Sciences; Cancer; carbohydrate metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Disease Models, Animal; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Fasting; Fat body; Gene Deletion; Gene expression regulation; Glucose - metabolism; Homeostasis; Homozygote; Homozygotes; hormone receptors; insect growth; Insect larvae; insect physiology; Insects; Insulin; Insulin - genetics; insulin receptors; Insulin-like growth factors; insulin-like peptides; Larval development; Metabolic disorders; metabolism; mutants; Mutation; Peptides; Phagocytosis; protein-protein interactions; Receptors; Signal transduction; Sugars; Survival; Triglycerides - metabolism; Type 1 diabetes mellitus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0905083106

Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of "starvation in the midst of plenty," a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.