Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities |
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| Authors: | Hua Zhang Jingnan Liu Caroline R. Li Bahram Momen Ronald A. Kohanski Leslie Pick |
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| Affiliation: | aDepartment of Entomology.;bProgram in Molecular and Cell Biology, and ;cDepartment of Environmental Science and Technology, University of Maryland, College Park, MD 20742; and ;dDepartments of Pediatrics and Pharmacology, Johns Hopkins Medical Institutes, Baltimore, MD 21205 |
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| Abstract: | 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. |
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| Keywords: | diabetes DILP Drosophila insulin receptor insect physiology trehalose |
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