Exp Clin Endocrinol Diabetes 2013; 121 - OP5_30
DOI: 10.1055/s-0033-1336638

PI3K/mTOR signalling and IGF-binding protein 2 (IGFBP2) production in human adipocyte models

FK Wilhelm 1, 2, F Kässner 1, GL Schmid 1, 2, J Kratzsch 3, A Körner 1, W Kiess 1, A Garten 1
  • 1Universität Leipzig, Hospital for Children and Adolescents, Center for Pediatric Research Leipzig, Leipzig, Germany
  • 2Universität Leipzig, Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany
  • 3Universität Leipzig, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany

Aims: IGF-binding protein 2 (IGFBP2) is considered a marker for the status of PTEN (phosphatase and tensin homologue) and activity of the PI3K (phosphatidylinositol-3 kinase)/mTOR (mammalian target of rapamycin) pathway.

Aims: We evaluated IGFBP2 serum levels in a patient with a heterozygous germline PTEN deletion and PTEN-Hamartoma-Tumor-Syndrome (PHTS) who received an individual treatment with rapamycin. We wanted to analyse the influence of pharmacological inhibitors of the AKT/PI3K/mTOR pathway on IGFBP2 production during adipose differentiation.

Methods: IGFBP2 was measured in serum samples taken from the patient at every consultation. Preadipocyte cultures (LipPD1) from a resected lipoma of the patient and human control preadipocytes (SGBS, non-PTEN deficient lipoma cells Lip2) were differentiated in vitro and treated with the respective inhibitors.

Results: Elevated serum IGFBP2 levels were observed in the patient with PHTS. During rapamycin treatment IGFBP2 serum levels alternated but did not decrease significantly. We detected IGFBP2 mRNA and protein expression as well as secretion in all analysed human adipocyte models during differentiation. PTEN-deficient lipoma cells were found to produce IGFBP2 during in vitro differentiation in amounts comparable to the non-PTEN-deficient adipocyte models (4.6 ± 3.6 ng/ml released from LipPD1 vs. 4.1 ± 2.9 ng/ml from SGBS cells on day 4 of differentiation). Incubation with the AKT inhibitor perifosine and the PI3K inhibitor wortmannin caused a significant decrease in both IGFBP2 expression (5µM perifosine, 100µM wortmannin p < 0.05) and secretion (25µM perifosine, 10µM wortmannin p < 0.05). However, the mTOR complex1 inhibitor rapamycin had no significant effect on IGFBP2 production.

Conclusion: IGFBP2 production in our lipoma cell model seems not to be influenced by PTEN deficiency or by inhibition of mTOR complex1. Inhibition of PI3K or AKT decreased IGFBP2 expression and secretion in lipoma cells.