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PMID:19887630

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Citation

Zhang, H, Liu, J, Li, CR, Momen, B, Kohanski, RA and Pick, L (2009) Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities. Proc. Natl. Acad. Sci. U.S.A. 106:19617-22

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.

Links

PubMed PMC2780814 Online version:10.1073/pnas.0905083106

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:INSL2

involved_in

GO:0030307: positive regulation of cell growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:INSL2

involved_in

GO:0009758: carbohydrate utilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:INSL2

involved_in

GO:0070328: triglyceride homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:INSL2

involved_in

GO:0040018: positive regulation of multicellular organism growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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