We have identified a novel gene product differentially expressed in skeletal muscle in a rat diabetes model induced by streptozotocin. Northern blot analysis showed expression in all studied tissues and a marked down-regulation in insulin-sensitive tissues (skeletal muscle, myocardium) but not in insulin-insensitive brain. cDNA sequence analysis revealed an open reading frame (ORF) of 58 aminoacids, containing one putative transmembrane domain. We designated this protein DAPIT (diabetes-associated protein in insulin-sensitive tissues). Database searches discovered several human, rat, mouse, rabbit, bovine, equine, porcine, Fugu and Xenopus ESTs with significant homology in the ORF. The aminoacid sequence of DAPIT is similar to that of a putative protein of Drosophila melanogaster and to a aAMP-generating peptide isolated from the flesh by Neobellieria bullata. We propose that DAPIT is a novel protein that is highly conserved in vertebrates and insects.