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. 1998 Jul 15;17(14):3858–3866. doi: 10.1093/emboj/17.14.3858

PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus.

G Condorelli 1, G Vigliotta 1, C Iavarone 1, M Caruso 1, C G Tocchetti 1, F Andreozzi 1, A Cafieri 1, M F Tecce 1, P Formisano 1, L Beguinot 1, F Beguinot 1
PMCID: PMC1170721  PMID: 9670003

Abstract

We have used differential display to identify genes whose expression is altered in type 2 diabetes thus contributing to its pathogenesis. One mRNA is overexpressed in fibroblasts from type 2 diabetics compared with non-diabetic individuals, as well as in skeletal muscle and adipose tissues, two major sites of insulin resistance in type 2 diabetes. The levels of the protein encoded by this mRNA are also elevated in type 2 diabetic tissues; thus, we named it PED for phosphoprotein enriched in diabetes. PED cloning shows that it encodes a 15 kDa phosphoprotein identical to the protein kinase C (PKC) substrate PEA-15. The PED gene maps on human chromosome 1q21-22. Transfection of PED/PEA-15 in differentiating L6 skeletal muscle cells increases the content of Glut1 transporters on the plasma membrane and inhibits insulin-stimulated glucose transport and cell-surface recruitment of Glut4, the major insulin-sensitive glucose transporter. These effects of PED overexpression are reversed by blocking PKC activity. Overexpression of the PED/PEA-15 gene may contribute to insulin resistance in glucose uptake in type 2 diabetes.

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Selected References

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