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饮食诱导的胰岛素抵抗中颈动脉体功能障碍与形态改变有关。

Carotid Body Dysfunction in Diet-Induced Insulin Resistance Is Associated with Alterations in Its Morphology.

机构信息

CEDOC, Centro de Estudos Doenças Crónicas, Nova Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.

出版信息

Adv Exp Med Biol. 2018;1071:103-108. doi: 10.1007/978-3-319-91137-3_13.

DOI:10.1007/978-3-319-91137-3_13
PMID:30357740
Abstract

The carotid body (CB) is organized in clusters of lobules containing type I cells and type II cells, in a ratio of approximately 4:1. The CB undergoes structural and functional changes during perinatal development, in response to a variety of environmental stimuli and in pathological conditions. Knowing that the CB acts as a metabolic sensor involved in the control of peripheral insulin sensitivity and that its overactivation contributes to the genesis of metabolic disturbances, herein we tested if diet-induced insulin resistance is associated with morphological alterations in the proportion of type I and type II cells in the CB. Diet induced insulin resistant model (HFHSu) was obtained by submitting Wistar rats to 14 weeks of 60% lipid-rich diet and 35% of sucrose in drinking water. The HFHSu group was compared with an aged-matched control group. Glucose tolerance and insulin sensitivity were measured in conscious animals before diet administration and 14 weeks after the diet protocol. The expression of tyrosine hydroxylase (TH) and nestin were assessed by immunohistochemistry to identify type I and type II cells, respectively. TH expression was also quantified by Western blot. As expected, 14 weeks of HFHSu diet induced a decrease in insulin sensitivity as well as in glucose tolerance. HFHsu diet increased the number of TH-positive type I cells by 192% and decreased nestin-postive type 2 cells by 74%. This increase in type II cells observed by immunohistochemistry correlates with an increase by 107% in TH expression quantified by Western blot. These results suggest that changes in CB morphology are associated with metabolic disturbances invoked by administration of a hypercaloric diet.

摘要

颈动脉体(CB)由小叶簇组成,包含 I 型细胞和 II 型细胞,比例约为 4:1。CB 在围产期发育过程中会发生结构和功能变化,以响应各种环境刺激和病理条件。已知 CB 作为代谢传感器,参与外周胰岛素敏感性的控制,其过度激活导致代谢紊乱的发生,因此,我们在此测试饮食诱导的胰岛素抵抗是否与 CB 中 I 型和 II 型细胞比例的形态改变有关。通过让 Wistar 大鼠接受 14 周 60%脂质丰富的饮食和 35%蔗糖的饮用水,获得饮食诱导的胰岛素抵抗模型(HFHSu)。HFHSu 组与年龄匹配的对照组进行比较。在饮食前和饮食方案 14 周后,在清醒动物中测量葡萄糖耐量和胰岛素敏感性。通过免疫组织化学分别评估酪氨酸羟化酶(TH)和巢蛋白的表达以鉴定 I 型和 II 型细胞。通过 Western blot 还定量了 TH 的表达。正如预期的那样,14 周的 HFHSu 饮食导致胰岛素敏感性和葡萄糖耐量降低。HFHSu 饮食使 TH 阳性 I 型细胞数量增加了 192%,nestin 阳性 II 型细胞减少了 74%。通过免疫组织化学观察到的 II 型细胞增加与 Western blot 定量的 TH 表达增加 107%相关。这些结果表明,CB 形态的变化与高热量饮食引起的代谢紊乱有关。

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