Hong Jing, Jeppesen Per Bendix, Nordentoft Iver, Hermansen Kjeld
Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
Diabetes Metab Res Rev. 2007 Mar;23(3):202-10. doi: 10.1002/dmrr.663.
While the effect of fatty acids and ectopic triglyceride storage in pancreatic beta cells has been well-defined, only limited information is available on alpha cells. This study evaluates the long-term impact of fatty acids on alpha cell function and proliferation as well as fatty acid oxidation.
Clonal alpha cells were cultured with fatty acids in the presence of high glucose for up to 3 days. The influence of fatty acids on glucagon secretion, glucagon content and triglyceride accumulation from 24 to 72 h was investigated. After a - 72 h culture, cell proliferation, carnitine palmitoyl transferase-1 mRNA level and the effect of etomoxir were also elucidated.
Fatty acids stimulated glucagon secretion and increased triglyceride accumulation in a time- and dose-dependent manner, but inhibited alpha cell proliferation. Lower concentrations (0.125-0.25 mM) of fatty acids significantly increased glucagon secretion at 48 and 72 h, but did not affect triglyceride content. However, a marked increment in triglyceride accumulation occurred in the presence of 0.5 mM fatty acids. Fatty acids caused an up-regulation of the expression of carnitine palmitoyl transferase-1 gene. Etomoxir (1 microM) reversed fatty acid-induced glucagon hypersecretion, but did not inhibit carnitine palmitoyl transferase-1 mRNA level.
Our data indicates that compared with triglyceride accumulation, glucagon secretion is more sensitive to changes in fatty acid concentration. The effect of fatty acids on the glucagon response is mediated through their oxidation. The high carnitine palmitoyl transferase-1 gene expression and the accumulation of triglyceride may initially be a compensatory oxidation reaction to elevated fatty acids.
虽然脂肪酸和异位甘油三酯在胰腺β细胞中的储存作用已得到明确，但关于α细胞的相关信息却十分有限。本研究评估了脂肪酸对α细胞功能、增殖以及脂肪酸氧化的长期影响。
将克隆的α细胞在高糖环境下与脂肪酸共同培养长达3天。研究了脂肪酸在24至72小时内对胰高血糖素分泌、胰高血糖素含量和甘油三酯积累的影响。在72小时培养后，还阐明了细胞增殖、肉碱棕榈酰转移酶-1 mRNA水平以及依托莫昔的作用。
脂肪酸以时间和剂量依赖的方式刺激胰高血糖素分泌并增加甘油三酯积累，但抑制α细胞增殖。较低浓度（0.125 - 0.25 mM）的脂肪酸在48和72小时时显著增加胰高血糖素分泌，但不影响甘油三酯含量。然而，在0.5 mM脂肪酸存在的情况下，甘油三酯积累显著增加。脂肪酸导致肉碱棕榈酰转移酶-1基因表达上调。依托莫昔（1 microM）可逆转脂肪酸诱导的胰高血糖素分泌过多，但不抑制肉碱棕榈酰转移酶-1 mRNA水平。
我们的数据表明，与甘油三酯积累相比，胰高血糖素分泌对脂肪酸浓度变化更敏感。脂肪酸对胰高血糖素反应的影响是通过其氧化介导的。高肉碱棕榈酰转移酶-1基因表达和甘油三酯积累最初可能是对脂肪酸升高的一种代偿性氧化反应。
