Laviola Luigi, Perrini Sebastio, Cignarelli Angelo, Natalicchio Annalisa, Leonardini Anna, De Stefano Francesca, Cuscito Marilena, De Fazio Michele, Memeo Vincenzo, Neri Vincenzo, Cignarelli Mauro, Giorgino Riccardo, Giorgino Francesco
Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology and Metabolic Diseases, University of Bari, Piazza Giulio Cesare, 11, I-70124 Bari, Italy.
Diabetes. 2006 Apr;55(4):952-61. doi: 10.2337/diabetes.55.04.06.db05-1414.
In this study, we evaluated the activation of various insulin signaling molecules in human fat in vivo and compared signaling reactions in visceral and subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies were obtained from nonobese subjects with normal insulin sensitivity under basal conditions and 6 and 30 min following administration of intravenous insulin. Insulin receptor phosphorylation was more intense and rapid and insulin receptor protein content was greater in omental than in subcutaneous adipose tissue (P < 0.05). Insulin-induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of significant changes in Akt protein content. Accordingly, phosphorylation of the Akt substrate glycogen synthase kinase-3 was more responsive to insulin stimulation in omental fat. Protein content of extracellular signal-regulated kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P < 0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in contrast with a more gradual increase observed in subcutaneous fat. In conclusion, the adipocyte insulin signaling system of omental fat shows greater and earlier responses to insulin than that of subcutaneous fat. These findings may contribute to explain the biological diversity of the two fat depots.
在本研究中，我们评估了人体脂肪中各种胰岛素信号分子的激活情况，并比较了内脏和皮下脂肪库中的信号反应。在基础条件下以及静脉注射胰岛素后6分钟和30分钟，从胰岛素敏感性正常的非肥胖受试者获取配对的腹部网膜和皮下脂肪活检样本。网膜脂肪组织中胰岛素受体磷酸化比皮下脂肪组织更强烈、更迅速，且胰岛素受体蛋白含量更高（P < 0.05）。在Akt蛋白含量无显著变化的情况下，胰岛素诱导的Akt磷酸化在网膜脂肪中也比皮下脂肪发生得程度更大且更早（P < 0.05）。因此，Akt底物糖原合酶激酶-3的磷酸化对网膜脂肪中的胰岛素刺激反应更敏感。细胞外信号调节激酶（ERK）-1/2的蛋白含量在网膜脂肪中比皮下脂肪高3倍（P < 0.05），并且ERK磷酸化在网膜脂肪中在6分钟时出现早期峰值，而在皮下脂肪中观察到的增加则较为缓慢。总之，网膜脂肪的脂肪细胞胰岛素信号系统对胰岛素的反应比皮下脂肪更大且更早。这些发现可能有助于解释这两个脂肪库的生物学差异。
