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Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

International Journal of Obesity volume 32, pages 1705–1711 (2008)Cite this article

Abstract

Objective:

To establish that human adipocytes express functional glucose-dependent insulinotropic peptide (GIP) receptors and in particular the regulation of GIP receptor (GIPR) expression in the context of the dynamic process of adipocyte differentiation.

Design:

A combination of semiquantitative real-time PCR and measurement of GIP-stimulated cAMP accumulation was used to establish the expression and functional coupling of GIPRs during in vitro differentiation of human Simpson–Golabi–Behmel syndrome (SGBS) preadipocytes.

Results:

Semiquantitative real-time PCR revealed that GIPR expression was substantially increased by day 4 of differentiation, reaching a maximum around 6–8 days (∼200-fold increase above undifferentiated cells, n=2). We also analysed the expression of the adipocyte fatty acid binding protein (FABP4) to relate GIPR expression to a molecular differentiation marker of adipogenesis. FABP4 expression was barely detectable in undifferentiated cells. However, following exposure to adipogenic medium, FABP4 expression gradually increased, with a maximal expression level around 10 days (∼1 600 000-fold increase above undifferentiated cells, n=2). Thus, the increases in GIPR mRNA during adipogenesis occur earlier than FABP4, suggesting that it might represent a gene expressed early in terminal differentiation and thus plays a role in fat droplet formation. A unit of 1 μM GIP failed to raise intracellular cAMP levels above basal levels in undifferentiated cells (n=3). In stark contrast, the 9-day differentiated cells produced a robust concentration-dependent increase in cAMP accumulation following stimulation with GIP, with an EC50 value of 2.3 nM (n=3). The maximal response represented a 9–34-fold increase in cAMP accumulation above basal levels.

Conclusions:

This study demonstrates that GIPRs are expressed by human adipocytes, both GIPR mRNA and functional receptor expression being present in differentiated adipocytes but not in preadipocytes. Further investigation into the functional effects of GIP on differentiated SGBS cells could help towards understanding exactly how GIP regulates fat accumulation in human adipocytes.

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Acknowledgements

RE Weaver is the recipient of a BBSRC studentship.

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Authors and Affiliations

  1. Institute of Membrane and System Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK

    R E Weaver & D Donnelly

  2. Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany

    M Wabitsch

  3. Division of Cardiovascular and Diabetes Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK

    P J Grant & A J Balmforth

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  1. R E Weaver
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  2. D Donnelly
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Correspondence to A J Balmforth.

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Weaver, R., Donnelly, D., Wabitsch, M. et al. Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model. Int J Obes 32, 1705–1711 (2008). https://doi.org/10.1038/ijo.2008.148

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  • DOI: https://doi.org/10.1038/ijo.2008.148

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