• L Hansen, J N Jensen, C T Ekstrøm, H Vestergaard, T Hansen, and O Pedersen.
• Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
• Diabetologia. 2001 Feb 1; 44 (2): 237-40.

Aim/HypothesisPhosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein regulates the insulin-dependent phosphoinositide 3-kinase (PI3K) signalling cassette and accordingly might function as a regulator of insulin sensitivity in skeletal muscle and adipose tissue. In this study we tested PTEN as a candidate gene for insulin resistance and late-onset Type II (non-insulin-dependent) diabetes mellitus in a Danish Caucasian population.MethodsThe nine exons of the PTEN, including intronic flanking regions were analysed by PCR-SSCP and heteroduplex analysis in 62 patients with insulin-resistant Type II diabetes.ResultsNo mutations predicted to influence the expression or biological function of the PTEN protein but four intronic polymorphisms were identified: IVS1-96 A-->G (allelic frequency 0.22, 95 % CI: 0.12-0.32), IVS3 + 99 C-->T (0.01, CI: 0-0.03), IVS7-3 TT-->T (0.10, CI: 0.03-0.18) and IVS8 + 32 G-->T (0.35, CI: 0.23-0.47). The IVS8 + 32 G-->T polymorphism was used as a bi-allelic marker for the PTEN locus and examined in 379 patients with Type II diabetes and in 224 control subjects with normal glucose tolerance. The IVS8 + 32 G-->T polymorphism in the PTEN was not associated with Type II diabetes and it did not have any effect on body-mass index, blood pressure, HOMA insulin resistance index, or concentrations of plasma glucose, serum insulin or serum C peptide obtained during an oral glucose tolerance test (OGTT).Conclusion/InterpretationVariability in the PTEN is not a common cause of Type II diabetes in the Danish Caucasian population.

40 keywords...

hide…