Abstract

A set of 14 insulin-producing cells (IPCs) in the Drosophila brain produces three insulin-like peptides (DILP2, 3 and 5). Activity in IPCs and release of DILPs is nutrient dependent and controlled by multiple factors such as fat body-derived proteins, neurotransmitters, and neuropeptides. Two monoamine receptors, the octopamine receptor OAMB and the serotonin receptor 5-HT1A, are expressed by the IPCs. These receptors may act antagonistically on adenylate cyclase. Here we investigate the action of the two receptors on activity in and output from the IPCs. Knockdown of OAMB by targeted RNAi led to elevated Dilp3 transcript levels in the brain, whereas 5-HT1A knockdown resulted in increases of Dilp2 and 5. OAMB-RNAi in IPCs leads to extended survival of starved flies and increased food intake, whereas 5-HT1A-RNAi produces the opposite phenotypes. However, knockdown of either OAMB or 5-HT1A in IPCs both lead to increased resistance to oxidative stress. In assays of carbohydrate levels we found that 5-HT1A knockdown in IPCs resulted in elevated hemolymph glucose, body glycogen and body trehalose levels, while no effects were seen after OAMB knockdown. We also found that manipulations of the two receptors in IPCs affected male aggressive behavior in different ways and 5-HT1A-RNAi reduced courtship latency. Our observations suggest that activation of 5-HT1A and OAMB signaling in IPCs generates differential effects on Dilp transcription, fly physiology, metabolism and social interactions. However the findings do not support an antagonistic action of the two monoamines and their receptors in this particular system.

Highlights

  • Insulin and insulin-like growth factors (IGFs) are evolutionary conserved peptides that regulate development, growth and aspects of physiology in a broad range of animals [1,2,3,4,5,6,7,8,9]

  • With application of DILP2 antiserum to brains with octopaminergic and tyraminergic neurons marked by Tdc2Gal4 driven GFP, we found that some GFP-labeled branches superimpose those of the insulinproducing cells (IPCs) dendrites in the pars intercerebralis of the brain (Fig 1)

  • Our study shows that octopamine and serotonin differentially modulate the activity of brain IPCs in Drosophila via the receptors OAMB and 5-HT1A

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Summary

Introduction

Insulin and insulin-like growth factors (IGFs) are evolutionary conserved peptides that regulate development, growth and aspects of physiology in a broad range of animals [1,2,3,4,5,6,7,8,9]. In adult flies the activity in IPCs and production and release of DILPs is under control by fat body-derived diffusible molecules such as DILP6 and the leptin-like cytokine Unpaired 2 (Upd2) [20,21]. Systemic release of these factors from the fat body is nutrient-dependent. A portion of the GABAergic system in the pars intercerebralis seems to be inactivated by circulating Upd after feeding and thereby tonic inhibition of the IPCs is lifted (via the action of Jak/Stat signaling) which facilitates DILP release [20]

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