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Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells

International Journal of Obesity volume 24, pages 1246–1253 (2000)Cite this article

Abstract

OBJECTIVE: Previous studies have demonstrated that leptin can stimulate proliferation of insulin-secreting tumor cell lines. The objective of this study was to characterize whether leptin could stimulate proliferation of primary β-cells too. Since adult β-cells have very limited capacity for replication, we examined the effect of leptin on islets of Langerhans obtained from fetal rats, in a tissue culture system.

METHODS: Leptin receptor mRNA and c-fos mRNA were measured by RT-PCR. Proliferation of fetal rat islet cells was measured by a WST-1 colorimetric assay and [3H]-thymidine incorporation assay.

RESULTS: Leptin stimulated proliferation of serum-deprived fetal rat islet cells, as indicated by increased formation of formazan dye from a tetrazolium salt WST-1. Leptin stimulated DNA synthesis in islet cells, as indicated by increased [3H]-thymidine incorporation into DNA. The effect of leptin on islet cell proliferation was on average 39–50% of the effect obtained with 10% fetal bovine serum. Leptin increased c-fos mRNA expression by 2.8-fold in isolated fetal islets after 30 min treatment. In fetal pancreatic islets, both the common extracellular portion (OB-R) and the intact long form (OB-Rb) of the leptin receptor were readily detected by reverse transcriptase polymerase chain reaction.

CONCLUSION: Functional leptin receptors are expressed in pancreatic islet cells, as early as during the fetal stage of development of these microorgans. Leptin stimulates proliferation of fetal islet cells and might play a role in determining islet cell mass at birth.

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Acknowledgements

We are grateful to Elvi Sandberg for excellent help in preparing fetal pancreatic islets. This work was supported by grants from the Swedish Society of Medicine, the Foundations of the National Board of Health and Welfare, Barndiabetesfonden, Tore Nilsson's Foundation for Medical Research, Åke Wiberg's Fund, Novo-Nordisk Pharma AB, Torsten and Ragnar Söderberg's Foundation, Magnus Bergvall's Fund, the Swedish Medical Research Council, Harald Jeansson's Foundation, Harald and Greta Jeansson's Foundation and the Funds of the Karolinska Institutet. MSI is the recipient of Career Development Award from the Juvenile Diabetes Foundation International (JDFI).

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  1. Department of Molecular Medicine (MSI, Rolf Luft Center for Diabetes Research, AS), Karolinska Institutet, Karolinska Hospital, Stockholm, SE-171 76, Sweden

    MS Islam & Å Sjöholm

  2. Clore Laboratory (VE), University of Buckingham, Buckingham, MK18 1EG, UK

    V Emilsson

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  1. MS Islam
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  2. Å Sjöholm
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  3. V Emilsson
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Correspondence to MS Islam.

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Islam, M., Sjöholm, Å. & Emilsson, V. Fetal pancreatic islets express functional leptin receptors and leptin stimulates proliferation of fetal islet cells. Int J Obes 24, 1246–1253 (2000). https://doi.org/10.1038/sj.ijo.0801370

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