Abstract
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 far from understood. Previous work has shown that dilp1/DILP1 is transiently expressed mainly during the pupal stage and the first days of adult life. Here, we study the role of dilp1 in the pupa, as well as in the first week of adult life, and make some comparisons to dilp6 that displays a similar pupal expression profile, but is expressed in fat body rather than brain neurosecretory cells. We show that mutation of dilp1 diminishes organismal weight during pupal development, whereas overexpression increases it, similar to dilp6 manipulations. No growth effects of dilp1 or dilp6 manipulations were detected during larval development. We next show that dilp1 and dilp6 increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. Effects of dilp1 manipulations can also be seen in the adult fly. In newly eclosed female flies, survival during starvation is strongly diminished in dilp1 mutants, but not in dilp2 and dilp1/dilp2 mutants, whereas in older flies, only the double mutants display reduced starvation resistance. Starvation resistance is not affected in male dilp1 mutant flies, suggesting a sex dimorphism in dilp1 function. Overexpression of dilp1 also decreases survival during starvation in female flies and increases egg laying and decreases egg to pupal viability. In conclusion, dilp1 and dilp6 overexpression promotes metabolism and growth of adult tissues during the pupal stage, likely by utilization of stored lipids. Some of the effects of the dilp1 manipulations may carry over from the pupa to affect physiology in young adults, but our data also suggest that dilp1 signaling is important in metabolism and stress resistance in the adult stage.
Highlights
The insulin/IGF signaling (IIS) pathway plays a central role in nutrient-dependent growth control during development, as well as in adult physiology and aging [1,2,3,4,5]
It was previously reported that decreased dilp1 activity reduces adult body weight in Drosophila, but it was not investigated at what developmental stage this occurred or whether the weight decrease was caused by diminished organismal growth [11, 20]
In dilp1 mutant pupae, the mRNA levels of dilp2, dilp3, and dilp6 were not altered, but in dilp6 mutants, the dilp1 level was upregulated (Supplementary Figures 1A–C). These findings suggest that only minor compensatory changes in transcripts of other dilps in dilp1 mutants occur during the mid-pupal stage
Summary
The insulin/IGF signaling (IIS) pathway plays a central role in nutrient-dependent growth control during development, as well as in adult physiology and aging [1,2,3,4,5]. In mammals, insulin, IGFs, and relaxins act on different types of receptors to regulate metabolism, growth, and reproduction [6,7,8,9]. This class of peptide hormones has been well conserved over evolution and the genetically tractable fly Drosophila is an attractive model system for investigating IIS mechanisms [1, 10, 11]. Genetic ablation of the IPCs reduces growth and alters metabolism, and results in increased resistance to several forms of stress and prolongs lifespan [19, 21]
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