Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) that are involved in the regulation of carbohydrate concentrations in hemolymph as well as in accumulation of storage metabolites. In the present study, we investigated diet-dependent roles of DILPs encoded by the genes dilp1–5, and dilp7 in the regulation of insect appetite, food choice, accumulation of triglycerides, glycogen, glucose, and trehalose in fruit fly bodies and carbohydrates in hemolymph. We have found that the wild type and the mutant lines demonstrate compensatory feeding for carbohydrates. However, mutants on dilp2,3, dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast diets. To evaluate metabolic differences between studied lines on different diets we applied response surface methodology. High nutrient diets led to a moderate increase in concentration of glucose in hemolymph of the wild type flies. Mutations on dilp genes changed this pattern. We have revealed that the dilp2 mutation led to a drop in glycogen levels independently on diet, lack of dilp3 led to dramatic increase in circulating trehalose and glycogen levels, especially at low protein consumption. Lack of dilp5 led to decreased levels of glycogen and triglycerides on all diets, whereas knockout on dilp7 caused increase in glycogen levels and simultaneous decrease in triglyceride levels at low protein consumption. Fruit fly appetite was influenced by dilp3 and dilp7 genes. Our data contribute to the understanding of Drosophila as a model for further studies of metabolic diseases and may serve as a guide for uncovering the evolution of metabolic regulatory pathways.

Insulin‐like peptides (ILPs) belong to the insulin superfamily and act as hormones, neuromediators, and growth factors during the post‐embryonic life‐cycle stages of insects. These peptides are encoded by different genes in various species. In the genus Drosophila, eight peptides are known, seven of which are likely to bind the Drosophila insulin receptor, whereas DILP8 is a known ligand of the Lgr3 receptor. Binding of DILPs 1‐7 to receptors leads to activation of intracellular proteins related to the conserved insulin/IGF (insulin‐like growth factors) signaling pathway. The insulin pathway acts within a complex physiological regulatory network involved in the coordination of development, growth, behavior, metabolism, lifespan, and cognitive functions in insects. The current review summarizes recent data about the structure and function of ILPs in fruit flies. The role of environmental factors and genetic manipulations in modulating the functions of DILPs and their association with lifespan and metabolism of Drosophila are assessed. Further investigation and identification of pharmacological or biotechnological interventions that may decrease insulin/IGF signaling could be a highly promising approach for extension of human health span and longevity.

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Nutrition affects various life-history traits. We used fruit flies Drosophila melanogaster to determine whether life-history traits, particularly life span and metabolism, are affected by dietary sucrose content. We fed flies by four different diets containing constant yeast concentration and increasing amounts of sugar ranged from 1% to 20%. We found that low sucrose diet increases female lifespan. We also showed, that low dietary sucrose maximized malate dehydrogenase, aspartate aminotransferase activity in males and lactate dehydrogenase activity in females. In addition, dietary carbohydrate has a considerable impact on urea level, suggesting that dietary carbohydrate impacts overall metabolism. Our findings revealed the influence of dietary sugar on metabolic enzymes activities, indicating an existence of optimal nutritional conditions for prolongevity phenotype and confirming an important impact of dietary sugar on life-history traits.

Interventions such as caloric or dietary restriction extend lifespan in organisms spanning from yeast to primates. Despite its positive influence on longevity, dietary restriction has been found to negatively affect reproduction. Many studies have reported negative correlations between lifespan and reproductive characteristics (such as mating rate, fecundity, reproductive period, and others). Such correlation gives the appearance of a resource-based trade-off between these two life-history traits. Here, we have used nutritional geometry to confirm previous findings in flies that dietary macronutrient balance (protein-to-carbohydrate ratio, P:C) impacts both lifespan and reproduction, such that across a series of diets differing in P:C, maximum lifespan was observed at a lower P:C (1:8) than that which supported highest fecundity (1:1.5). We have then addressed the question whether variation among Drosophila melanogaster Meigen (Diptera: Drosophilidae) fruit flies in food intake and egg production within a single dietary treatment is negatively associated with within-diet variation in lifespan, as might be expected under a resource-based trade-off. There was no such association between intake rate, egg production, and longevity. We noted that the smaller sample sizes and smaller inter-individual variance apparent within -as compared to across -diet treatments may have weakened any signature of a trade-off between lifespan and reproduction. Thus, we conclude that, whereas dietary macronutrient ratio is a primary determinant of both reproduction and longevity, neither eating less nor laying fewer eggs per se predicted lifespan. This supports the view that there is not a simple quantitative resource-based trade-off between lifespan and reproduction, but rather these represent life-history traits with qualitatively different nutritional optima.

The insulin–IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in Drosophila melanogaster, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the Drosophila transcripts for the insulin-like peptides dilp2, dilp5, and dilp6. This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (tobi). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, Pten knockdown to enhance IIS also activated JAK–STAT signaling in gut tissue by up-regulation of upd2, upd3, and soc36 genes, as well as genes encoding the EGF receptor ligands spitz and vein. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival.

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