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


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.

SUBMITTER: Condorelli G 

PROVIDER: S-EPMC1170721 | biostudies-other | 1998 Jul

REPOSITORIES: biostudies-other

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

Condorelli G G   Vigliotta G G   Iavarone C C   Caruso M M   Tocchetti C G CG   Andreozzi F F   Cafieri A A   Tecce M F MF   Formisano P P   Beguinot L L   Beguinot F F  

The EMBO journal 19980701 14


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 diab  ...[more]

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