Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities.
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.
Zhang
Hua
H
Department of Entomology, University of Maryland, College Park, MD 20742, USA.
Liu
Jingnan
J
Li
Caroline R
CR
Momen
Bahram
B
Kohanski
Ronald A
RA
Pick
Leslie
L
D000818:Animals; D001343:Autophagy; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D006720:Homozygote; D007328:Insulin / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
D029721:Drosophila Proteins; D007328:Insulin; D014280:Triglycerides; D005947:Glucose