RRC ID 11646
著者 Zhang H, Liu J, Li CR, Momen B, Kohanski RA, Pick L.
タイトル Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 106(46)
ページ 19617-22
公開日 2009-11-17
DOI 10.1073/pnas.0905083106
PII 0905083106
PMID 19887630
PMC PMC2780814
MeSH Animals Autophagy* Diabetes Mellitus, Type 1 / genetics Diabetes Mellitus, Type 1 / metabolism Disease Models, Animal Drosophila Proteins / genetics* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism* Gene Deletion Glucose / metabolism Homozygote Insulin / genetics* Triglycerides / metabolism
IF 9.412
引用数 96
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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