Phosphatidylinositol 3-kinase (PI3K) signalling regulates insulin-like-growth factor binding protein-2 (IGFBP-2) production in human adipocytes. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Wilhelm, Franziska; Kässner, Franziska; Schmid, Gordian; Kratzsch, Jürgen; Laner, Andreas; Wabitsch, Martin; Körner, Antje; Kiess, Wieland; Garten, Antje
• Is Part Of: Growth hormone & IGF research. Volume 25:Issue 3(2015:Jun.)
• Page Start: 115
• Page End: 120
• Publication Date: 2015-06
• Subjects: aP2 adipocyte protein 2 -- IGF insulin-like-growth factor -- IGFBP-2 insulin-like-growth factor binding protein-2 -- MEK mitogen-activated protein kinase kinase -- mTOR mammalian target of rapamycin -- PHTS PTEN hamartoma tumour syndrome -- PI3K phosphatidylinositol 3-kinase -- PTEN phosphatase and tensin homolog; Human adipocytes -- IGFBP-2 -- PTEN -- PHTS -- PI3K -- Rapamycin; Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2015.03.003
• Languages: English
• ISSNs: 1096-6374

Abstract

Abstract: Objective: Insulin-like-growth factor binding protein 2 (IGFBP-2) is thought to be a marker for the phosphatase and tensin homolog (PTEN) status and activity of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. We aimed to evaluate whether or not lipoma cells of a patient with a heterozygous deletion in the PTEN gene would produce more IGFBP-2 than PTEN non deficient control cells. Moreover, we analysed the influence of pharmacological inhibitors of the PI3K/AKT/mTOR pathway on IGFBP-2 production. Design: PTEN deficient preadipocytes and control PTEN non deficient preadipocytes were differentiated in vitro and treated with the respective inhibitors. PTEN was transiently down regulated by siRNA in human preadipocytes. IGFBP-2 mRNA and protein expression and IGFBP-2 in culture supernatant were measured. Results: PTEN deficient lipoma cells were found to produce IGFBP-2 during in vitro differentiation in comparable amounts to PTEN non deficient cells. In contrast, acute down regulation of PTEN in preadipocytes resulted in enhanced production of IGFBP-2. Incubation with the PI3K inhibitors LY294002 and wortmannin decreased IGFBP-2 mRNA and protein. Neither the mTOR complex 1 inhibitor rapamycin nor PD98059, an inhibitor of MEK (mitogen-activated protein kinase kinase), showed a significant effect on IGFBP-2 production. Conclusion: IGFBP-2 production in PTEN deficient preadipocytes was not influenced by PTEN deficiency or by inhibition of mTORC1 and MAPK. In contrast, inhibition of PI3K decreased IGFBP-2 expression and secretion. Highlights: Human adipocytes secrete IGFBP2 in the early phase of adipose differentiation. A heterozygous PTEN deletion does not influence IGFBP2 production in vitro siRNA-mediated knock down of PTEN leads to an increase in IGFBP2 secretion. Pharmacological inhibition of PI3K leads to a decrease in IGFBP2 production.