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

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.

authors

Zhang H,Liu J,Li CR,Momen B,Kohanski RA,Pick L

doi

10.1073/pnas.0905083106

subject

Has Abstract

pub_date

2009-11-17 00:00:00

pages

19617-22

issue

46

eissn

0027-8424

issn

1091-6490

pii

0905083106

journal_volume

106

pub_type

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