Regulatory Roles of Insulin-Like Peptide 1 (DILP1) in Metabolism Differ in Pupal and Adult 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 , 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 is transiently expressed mainly during the pupal stage and the first days of adult life. Here, we study the role of in the pupa, as well as in the first week of adult life, and make some comparisons to that displays a similar pupal expression profile, but is expressed in fat body rather than brain neurosecretory cells. We show that mutation of diminishes organismal weight during pupal development, whereas overexpression increases it, similar to manipulations. No growth effects of or manipulations were detected during larval development. We next show that and increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. Effects of manipulations can also be seen in the adult fly. In newly eclosed female flies, survival during starvation is strongly diminished in mutants, but not in and / mutants, whereas in older flies, only the double mutants display reduced starvation resistance. Starvation resistance is not affected in male mutant flies, suggesting a sex dimorphism in function. Overexpression of also decreases survival during starvation in female flies and increases egg laying and decreases egg to pupal viability. In conclusion, and overexpression promotes metabolism and growth of adult tissues during the pupal stage, likely by utilization of stored lipids. Some of the effects of the manipulations may carry over from the pupa to affect physiology in young adults, but our data also suggest that signaling is important in metabolism and stress resistance in the adult stage.