The role of central corticotrophin‐releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie‐restricted mice
The role of central corticotrophin‐releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie‐restricted mice
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DOI：
10.1111/jne.12961
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发表时间：
2021-03
影响因子：
3.2
通讯作者：
R. Kimura;Daisuke Kondo;Shota Takemi;M. Fujishiro;S. Tsukahara;T. Sakai;I. Sakata
中科院分区：
文献类型：
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作者：
R. Kimura;Daisuke Kondo;Shota Takemi;M. Fujishiro;S. Tsukahara;T. Sakai;I. Sakata
在严格的卡路里限制（CR）下，小鼠的胃饥饿素-生长激素轴参与维持血浆葡萄糖水平。胃饥饿素是一种来源于胃的酰化肽，在负能量状态下受交感神经上调。中枢促肾上腺皮质激素释放因子受体（CRF - R）信号刺激交感神经张力。本研究旨在研究在胃饥饿素参与下，中枢CRF - R信号对严重卡路里限制小鼠血浆葡萄糖浓度维持的影响。脑室内注射尿激酶- 1和尿激酶- 2 （CRF - R1和CRF - R2的天然配体），血浆胃饥饿素浓度升高和体外循环注射尿激酶- 1胃饥饿素升高可通过阿替洛尔（β1肾上腺素能受体拮抗剂）消除。然后，我们建立了一个60% CR的小鼠模型，发现在60% CR的小鼠中给予[d‐Lys3]‐GHRP‐6（一种生长素受体拮抗剂）比对照小鼠更能降低血浆葡萄糖浓度。同样，在CR低于60%的小鼠中，阿替洛尔注射显著降低了血浆葡萄糖浓度，这是由胃饥饿素共同给予的。在CR低于60%的小鼠中，静脉注射α螺旋CRH（一种非选择性促肾上腺皮质激素释放因子受体拮抗剂）可显著降低血浆葡萄糖浓度，尽管α螺旋CRH与胃促生长素联合使用可维持血糖水平。这些结果表明，中枢CRF - R信号通过交感神经生长素通路参与严重CR小鼠血浆葡萄糖水平的维持。
Under severe calorie restriction (CR), the ghrelin‐growth hormone axis in mice is involved in the maintenance of plasma glucose levels. Ghrelin, a stomach‐derived acylated peptide, is up‐regulated by the sympathetic nerve in the negative energy status. Central corticotrophin‐releasing factor receptor (CRF‐R) signalling stimulates the sympathetic tone. The present study aimed to examine the effect of central CRF‐R signalling on the maintenance of plasma glucose concentrations in severe calorie‐restricted mice with the involvement of ghrelin. Intracerebroventricular injections of urocorin‐1 and urocorin‐2, which are natural ligands for CRF‐R1 and CRF‐R2, elevated plasma ghrelin concentrations and ghrelin elevation with an i.c.v. injection of urocorin‐1 was cancelled by atenolol (β1 adrenergic receptor antagonist) administration. We then established a mice model of 60% CR and found that the administration of [d‐Lys3]‐GHRP‐6 (a ghrelin receptor antagonist) in mice under 60% CR reduced the plasma glucose concentration more compared to the vehicle mice. Similarly, the atenolol injection in mice under 60% CR significantly reduced the plasma glucose concentration, which was rescued by the co‐administration of ghrelin. An i.c.v. injection of the alpha helical CRH, a non‐selective corticotrophin‐releasing factor receptor antagonist, in mice under 60% CR significantly reduced the plasma glucose concentration, although the co‐administration of α‐helical CRH with ghrelin maintained plasma glucose levels. These results suggest that central CRF‐R signalling is involved in the maintenance of plasma glucose levels in mice under severe CR via the sympathetic‐ghrelin pathway.