Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity inDrosophila

Abstract

Insulin signaling pathways are implicated in several physiological processes in invertebrates, including the control of growth and life span; the latter of these has also been correlated with juvenile hormone (JH) deficiency. In turn, JH levels have been correlated with sex-specific differences in locomotor activity. Here, the involvement of the insulin signaling pathway in sex-specific differences in locomotor activity was investigated in Drosophila. Ablation of insulin-producing neurons in the adult pars-intercerebralis was found to increase trehalosemia and to abolish sexual dimorphism relevant to locomotion. Conversely, hyper-insulinemia induced by insulin injection or by over-expression of an insulin-like peptide decreases trehalosemia but does not affect locomotive behavior. Moreover, we also show that in the head of adult flies, the insulin receptor (InR) is expressed only in the fat body surrounding the brain. While both male and female InR mutants are hyper-trehalosemic, they exhibit similar patterns of locomotor activity. Our results indicate that first, insulin controls trehalosemia in adults, and second, like JH, it controls sex-specific differences in the locomotor activity of adult Drosophila in a manner independent of its effect on trehalose metabolism.

Partial ablation of adult Drosophilainsulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance

“…We next investigated whether fasting hyperglycemia and glucose intolerance measured in adult IPC KD flies is associated with insulin resistance as is often seen in type 2 diabetes. 19 To approach this question, we developed an insulin tolerance assay in the adult fly based on mammalian procedures 20 where adult flies were injected with bovine insulin 21 followed by hemolymph extraction and glucose measurements. As shown in Figure 2A, a 29% decease in circulating glucose levels was measured as the result of insulin injection in control flies raised on RU-486 containing diet for 14 days whereas a comparable, 22% decease in circulating glucose levels was measured as the result of insulin injection in adult IPC KD flies (under RU-486 induction).…”

“…Experimental groups were injected with 0.1 ml of 0.01 mg/ml bovine insulin (Sigma) in PBS whereas control groups were injected with 0.1 ml of PBS alone. 21 Injected flies were allowed to recover in vials containing 1% agar for 5' or 30' before subjected to hemolymph extraction and glucose measurements. For each experiment, triplicates of 4 flies were injected and measured for hemolymph glucose levels.…”

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

“…Less clear is whether mosquito and other insect ILPs have overlapping activities and how activity may be regulated when only one IR/IGFR homolog and fewer isoforms of downstream signaling components are present (8,9). Genetic ablation of MNCs and the Drosophila IR (DIR) in Drosophila indicate that ILPs from the nervous system have metabolic and cell growth activity but do not reveal whether specific ILPs have differing biological activities (38)(39)(40)(41). Genetic studies also show that the DIR predominantly stimulates the PI3K/AKT pathway although some data also suggest activation of the MAPK pathway (7).…”

Natural variation in Drosophila melanogaster diapause due to the insulin-regulated PI3-kinase

“…This genetic correlation could be explained by pleiotropic effects of the Dp110 gene. Notably, mutational analyses of the insulinregulated PI3-kinase and other genes in the insulin-signaling pathway in D. melanogaster have revealed affects on lifespan (20)(21)(22), development (22), body size and growth (23,24), nutrient stress (25), lipid content (26), locomotor activity (27), and egg chamber development (28). Our findings suggest that Dp110 is not only an important regulator of diapause in D. melanogaster but also, through its pleiotropic effects, may influence the suite of life-history trade-offs associated with diapause in natural populations.…”