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首页> 外文期刊>Cell metabolism >Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis
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Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis

机译:棕榈酸羟基酸激活GPR40,其参与其对葡萄糖稳态的有益作用

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摘要

Palmitic acid hydroxystearic acids (PAHSAs) are endogenous lipids with anti-diabetic and anti-inflammatory effects. PAHSA levels are reduced in serum and adipose tissue of insulin-resistant people and high-fat diet (HFD)-fed mice. Here, we investigated whether chronic PAHSA treatment enhances insulin sensitivity and which receptors mediate PAHSA effects. Chronic PAHSA administration in chow-and HFD-fed mice raises serum and tissue PAHSA levels similar to 1.4-to 3-fold. This improves insulin sensitivity and glucose tolerance without altering body weight. PAHSA administration in chow-fed, but not HFD-fed, mice augments insulin and glucagon-like peptide (GLP-1) secretion. PAHSAs are selective agonists for GPR40, increasing Ca+2 flux, but not intracellular cyclic AMP. Blocking GPR40 reverses improvements in glucose tolerance and insulin sensitivity in PAHSA-treated chow-and HFD-fed mice and directly inhibits PAHSA augmentation of glucose-stimulated insulin secretion in human islets. In contrast, GLP-1 receptor blockade in PAHSA-treated chow-fed mice reduces PAHSA effects on glucose tolerance, but not on insulin sensitivity. Thus, PAHSAs activate GPR40, which is involved in their beneficial metabolic effects.
机译:棕榈酸羟基酸(PAHSA)是具有抗糖尿病和抗炎作用的内源性脂质。胰岛素抗性人和高脂饮食(HFD)-Fed小鼠的血清和脂肪组织减少了Pahsa水平。在这里,我们调查了慢性Pahsa治疗是否增强了胰岛素敏感性,受体介导PAHSA效应。 Chow-and HFD喂养小鼠中的慢性Pahsa管理将血清和组织Pahsa水平提高至1.4至3倍。这改善了胰岛素敏感性和葡萄糖耐受性而不改变体重。 Pahsa在Chow-Fed中管理,但没有HFD喂养,小鼠的小鼠增强胰岛素和胰高血糖素样肽(GLP-1)分泌。 Pahsas是针对GPR40的选择性激动剂,增加Ca + 2助焊剂,但不是细胞内循环放大器。阻断GPR40反转葡萄糖耐受性和胰岛素敏感性的改善,并直接抑制人胰岛中葡萄糖刺激的胰岛素分泌的PAHSA增强。相比之下,Pahsa处理的鸡肉饲料小鼠的GLP-1受体阻断降低了对葡萄糖耐受性的PAHSA影响,但不是胰岛素敏感性。因此,PAHSAS激活GPR40,涉及其有益的代谢效应。

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  • 来源
    《Cell metabolism》 |2018年第2期|共13页
  • 作者单位

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Salk Inst Biol Studies Helmsley Ctr Genom Med Clayton Fdn Labs Peptide Biol 10010 North Torrey;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Univ Calif San Diego Skaggs Sch Pharm &

    Pharmaceut Sci 9500 Gilman Dr La Jolla CA 92093 USA;

    Univ Cambridge Metab Res Labs Cambridge CB2 0QQ England;

    Univ Cambridge Metab Res Labs Cambridge CB2 0QQ England;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

    Salk Inst Biol Studies Helmsley Ctr Genom Med Clayton Fdn Labs Peptide Biol 10010 North Torrey;

    Beth Israel Deaconess Med Ctr Dept Med Div Endocrinol Diabet &

    Metab Room 747 330 Brookline Ave;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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