Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

Louise Torp Dalgaard, Peter Grevsen Thams, Louise Winkel Gaarn, Janne Jensen, Ying Chiu Lee, Jens Høiriis Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH’s suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages.
    Original languageEnglish
    JournalBiochemical and Biophysical Research Communications
    Volume410
    Issue number2
    Pages (from-to)345-350
    ISSN0006-291X
    DOIs
    Publication statusPublished - 2011

    Cite this

    Dalgaard, Louise Torp ; Thams, Peter Grevsen ; Gaarn, Louise Winkel ; Jensen, Janne ; Lee, Ying Chiu ; Nielsen, Jens Høiriis. / Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 410, No. 2. pp. 345-350.
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    abstract = "Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH’s suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages.",
    keywords = "FAT/CD36, beta-cell, lipotoxicity, growth hormone, lactogen, fatty acids, insulin secretion",
    author = "Dalgaard, {Louise Torp} and Thams, {Peter Grevsen} and Gaarn, {Louise Winkel} and Janne Jensen and Lee, {Ying Chiu} and Nielsen, {Jens H{\o}iriis}",
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    Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells. / Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel; Jensen, Janne; Lee, Ying Chiu; Nielsen, Jens Høiriis.

    In: Biochemical and Biophysical Research Communications, Vol. 410, No. 2, 2011, p. 345-350.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    AU - Dalgaard, Louise Torp

    AU - Thams, Peter Grevsen

    AU - Gaarn, Louise Winkel

    AU - Jensen, Janne

    AU - Lee, Ying Chiu

    AU - Nielsen, Jens Høiriis

    PY - 2011

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    N2 - Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH’s suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages.

    AB - Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH’s suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages.

    KW - FAT/CD36

    KW - beta-cell

    KW - lipotoxicity

    KW - growth hormone

    KW - lactogen

    KW - fatty acids

    KW - insulin secretion

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    JF - Biochemical and Biophysical Research Communications

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