Drosophila insulin-like peptide 1 (DILP1) promotes organismal growth during non-feeding stages

The insulin/IGF-signaling pathway is central in control of nutrient-dependent growth during development, and in adult physiology and longevity. Eight insulin-like peptides (DILP1-8) have been identified in Drosophila and several of these are known to regulate growth, metabolism, reproduction, stress responses and lifespan. However, the functional role of DILP1 is not fully understood. Previous work showed that dilp1/DILP1 is transiently expressed during the non-feeding pupal stage and the first days of adult life. Here we show that mutation of dilp1 diminishes organismal weight during pupal development, whereas overexpression increases it. Overexpression of dilp1 additionally increases body size of flies, but reduces stores of larval-derived energy, leading to increased feeding the first days after eclosion. No effects of dilp1 manipulations were detected during larval development. An earlier study demonstrated interactions between dilp1 and dilp2 in regulation of adult lifespan. Here we monitored the effects of dilp1, dilp2 and dilp1/dilp2 mutations on growth and found that only the single mutants displayed lower body mass. In recently eclosed flies, survival during starvation is strongly diminished in dilp1 mutants, but not in dilp2 and double mutants, whereas in older flies double mutants display reduced starvation resistance. Egg to pupal viability is decreased both after overexpression of dilp1, and in the double mutants. In conclusion, dilp1 promotes growth of adult tissues during the non-feeding pupal stage, likely due to reallocation of stored energy. This results in larger newly-eclosed flies with reduced stores of larval/pupal energy and diminished starvation tolerance and fecundity.