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The dysregulation of the hypothalamic–pituitary–adrenal axis in diet-induced prediabetic male Sprague Dawley rats
Nutrition & Metabolism ( IF 3.9 ) Pub Date : 2020-12-11 , DOI: 10.1186/s12986-020-00532-1
Palesa Mosili 1 , Bongeka Cassandra Mkhize 1 , Phikelelani Ngubane 1 , Ntethelelo Sibiya 2 , Andile Khathi 1
Affiliation  

Altered function of the hypothalamic–pituitary–adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Sprague Dawley Rats were randomly divided into non-pre-diabetic group (NPD) and pre-diabetic group (PD) (n = 6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were also measured. Impaired glucose handling in the PD group as well as increase in corticosterone was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed using the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.

中文翻译:

饮食诱导的糖尿病前期雄性斯普拉格道利大鼠下丘脑-垂体-肾上腺轴的失调

2 型糖尿病患者下丘脑-垂体-肾上腺 (HPA) 轴功能的改变(糖尿病前期的一种情况)已被证明会增加抑郁症的风险,并引起下游效应,导致糖异生上调和血脂异常。此外,压力,无论是来自管理糖尿病的心理压力还是与生活方式相关的压力,都会进一步激活 HPA 轴,导致过度的压力反应。本研究调查了选定的葡萄糖处理标志物中 HPA 轴的活性,以及​​饮食诱导的糖尿病前期大鼠模型中相对于 HPA 轴成分的应激反应。将 Sprague Dawley 大鼠随机分为非糖尿病前期组 (NPD) 和糖尿病前期组 (PD)(每组 n = 6),经过 20 周的诱导期和另外 12 周的实验期,获得 32几周。在 20 周和 32 周结束时,使用稳态模型评估指数测量葡萄糖处理、促肾上腺皮质激素 (ACTH) 和皮质酮 (CORT) 浓度。在为期12周的实验周中诱导应激并进行强迫游泳试验。32 周结束时,还测量了糖皮质激素和盐皮质激素海马受体。与 NPD 组相比,在 20 周和 32 周结束时观察到 PD 组的葡萄糖处理受损以及皮质酮增加。第20周时ACTH浓度没有观察到变化,而在第32周时,与NPD组相比,PD组中观察到血浆ACTH浓度降低。使用强迫游泳测试对应激诱导的动物施加压力:观察到的行为显示,与 NPD 组相比,PD 应激组的不动时间增加。随后观察到,与 NPD 应激组相比,PD 应激组的 ACTH 和 CORT 浓度降低。相对于应激 NPD 组,应激 PD 组的盐皮质激素和糖皮质激素受体基因表达升高。这些观察结果表明,饮食诱发的糖尿病前期与 HPA 轴活性受损和对压力的反应恶化有关。
更新日期:2020-12-11
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