Cloning of an insulin-dependent membrane aminopeptidase designated GTVap from GLUT-4 vesicles

摘要

The specification describes an aminopeptidase, designated GTVap, which cleaves insulin. GTVap has been purified from GLUT-4-containing vesicles and cloned. The peptidase has a measured mass of approximately 165 kD, but is 110 kD in its deglycosylated state. It has a predicted mass of 117,239 Daltons based on the amino acid sequence predicted from the cDNA of the figure (SEQ ID NOs: 15 and 16). It includes peptides having the amino acid sequences Phe-Ala-Ala-Thr-Gln-Phe-Glu-Pro-Leu-Ala-Ala (SEQ ID NO: 1) and Ile-Leu-Gln-Asn-Gln-Ile-Gln-Gln-Gln-Thr-Arg-Thr-Asp-Glu-Gly-Xaa-Pro-Xaa-Met (SEQ ID NO: 2), and binds with antibodies produced against the peptide identified as (SEQ ID NO: 1). Modulators of the activity of the aminopeptidase and a method for treating syndromes of insulin resistance, including diabetes, by administration of such a modulator are also claimed.