Cloning and characterization of the human and rat islet-specific glucose-8-phosphatase catalytic subunit-related protein (IGRP) genes

Islet-specific glucose-6-phosphatase (G6Pase) catalytic subunit-related pro tein (IGRP) is a homolog of the catalytic subunit of G6Pase, the enzyme tha t catalyzes the terminal step of the gluconeogenic pathway. Its catalytic a ctivity, however, has not been defined, Since IGRP gene expression is restr icted to islets, this suggests a possible role in the regulation of islet m etabolism and, hence, insulin secretion induced by metabolites. We report h ere a comparative analysis of the human, mouse, and rat IGRP genes. These s tudies aimed to identify conserved sequences that may be critical for IGRP function and that specify its restricted tissue distribution. The single co py human IGRP gene has five exons of similar length and coding sequence to the mouse IGRP gene and is located on human chromosome 2q28-32 adjacent to the myosin heavy chain 1B gene. In contrast, the rat IGRP gene does not app ear to encode a protein as a result of a series of deletions and insertions in the coding sequence. Moreover, rat IGRP mRNA, unlike mouse and human IG RP mRNA, is not expressed in islets or islet-derived cell lines, an observa tion that was traced by fusion gene analysis to a mutation of the TATA box motif in the mouse/human IGRP promoters to TGTA in the rat sequence. The re sults provide a framework for the further analysis of the molecular basis f or the tissue-restricted expression of the IGRP gene and the identification of key amino acid sequences that determine its biological activity.