Loss of endothelin type B receptor function improves insulin sensitivity in rats.
Loss of endothelin type B receptor function improves insulin sensitivity in rats.
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DOI：
10.1139/cjpp-2019-0666
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发表时间：
2020-02
影响因子：
2.1
通讯作者：
Osvaldo Rivera-Gonzalez;M. Kasztan;Jermaine G. Johnston;Kelly A. Hyndman;Joshua S. Speed
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文献类型：
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作者：
Osvaldo Rivera-Gonzalez;M. Kasztan;Jermaine G. Johnston;Kelly A. Hyndman;Joshua S. Speed
高盐摄入（HS）与肥胖和胰岛素抵抗有关。ET-1是一种响应HS而释放的肽，通过ET-1 B型（ET B）受体抑制胰岛素对培养的脂肪细胞的作用;然而，ET B受体活化对脂质代谢和胰岛素抵抗的体内影响尚不清楚。我们假设，响应于HS摄入的ETB受体的激活促进血脂异常和胰岛素抵抗。在正常盐（NS）喂养的大鼠中，对照组和ETB缺乏大鼠之间的体重或体脂量没有观察到显著差异。HS 2周后，与对照组相比，ETB def大鼠的体重和体脂量显著降低。基因型之间的非空腹血浆葡萄糖没有差异，然而，与对照组相比，ETB缺陷大鼠的血浆胰岛素浓度显著降低，表明胰岛素敏感性改善。此外，ETB缺乏大鼠在NS和HS组中都具有较高的循环游离脂肪酸，基因型之间的血浆甘油三酯没有差异。在另一项实验中，与对照组相比，ETB缺陷大鼠的空腹血糖显著降低，葡萄糖和胰岛素耐受性改善。这些数据表明，ET-1通过ETB受体促进脂肪沉积和胰岛素抵抗。
High salt intake (HS) is associated with obesity and insulin resistance. ET-1, a peptide released in response to HS, inhibits the actions of insulin on cultured adipocytes through ET-1 type B (ETB) receptors; however, the in vivo implications of ETB receptor activation on lipid metabolism and insulin resistance is unknown. We hypothesized that activation of ETB receptors in response to HS intake promotes dyslipidemia and insulin resistance. In normal salt (NS) fed rats, no significant difference in body weight or epidydimal fat mass was observed between control and ETB deficient rats. After 2 weeks of HS, ETB def rats had significantly lower body weight and epidydimal fat mass compared to controls. Non-fasting plasma glucose was not different between genotypes, however plasma insulin concentration was significantly lower in ETB deficient rats compared to controls suggesting improved insulin sensitivity. In addition, ETB deficient rats had higher circulating free fatty acids in both NS and HS groups, with no difference in plasma triglycerides between genotypes. In a separate experiment, ETB deficient rats had significantly lower fasting blood glucose and improved glucose and insulin tolerance compared to controls. These data suggest that ET-1 promotes adipose deposition and insulin resistance via the ETB receptor.