Inter-organ communication is essential for regulating development and homeostasis. Mutations in Drosophila Activin-Beta (Act-Beta) cause accelerated pupariation and reduced final body and organ size. To determine how Act-Beta affects size and timing, we first looked at which cells express Act-Beta and found expression in the Insulin Producing Cells (IPCs), neuroendocrine cells and motor neurons. Overexpression of Act-Beta in either neuroendocrine cells or motor neurons increases body size. Muscle-specific knockdown of the TGF-Beta signaling transducer/transcription factor dSmad2 reduces body size, indicating muscle is a target tissue of the Act-Beta signal. Additionally, levels of phospho-dSmad2 are reduced in skeletal muscle samples of Act-Beta mutants and increased in animals overexpressing Act-Beta from motor neurons. Levels of phospho-S6K in Act-Beta mutants are correlated with phospho-dSmad2 levels, suggesting TGF-Beta signaling regulates insulin signaling. Because insulin signaling controls metabolism, we used GC/MS analysis to identify and quantify levels of metabolites in whole-larval samples of Act-Beta mutants. We found intermediates of the energy-producing steps of glycolysis and lactic acid are reduced, indicating reduced flux through glycolysis. Overall, this indicates neuronally-derived Act-Beta signals to the skeletal muscle to regulate levels of insulin signaling and subsequent glycolysis. We have identified over 300 downstream targets of dSmad2 using RNA-seq of Act-Beta mutant skeletal muscle. We are testing impL2, an insulin binding protein, as a potential dSmad2 target gene regulating systemic insulin signaling.