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晚期地塞米松注射后改变的下丘脑-垂体-肾上腺轴的猪在低血糖钳夹期间单侧肾去神经支配后肾脏葡萄糖释放

Renal Glucose Release after Unilateral Renal Denervation during a Hypoglycemic Clamp in Pigs with an Altered Hypothalamic Pituitary Adrenal Axis after Late-Gestational Dexamethasone Injection.

机构信息

Orthopaedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany.

Institute for Biochemistry II, Jena University Hospital, 07743 Jena, Germany.

出版信息

Int J Mol Sci. 2023 Aug 13;24(16):12738. doi: 10.3390/ijms241612738.

Abstract

Previously, we demonstrated in pigs that renal denervation halves glucose release during hypoglycaemia and that a prenatal dexamethasone injection caused increased ACTH and cortisol concentrations as markers of a heightened hypothalamic pituitary adrenal axis (HPAA) during hypoglycaemia. In this study, we investigated the influence of an altered HPAA on renal glucose release during hypoglycaemia. Pigs whose mothers had received two late-gestational dexamethasone injections were subjected to a 75 min hyperinsulinaemic-hypoglycaemic clamp (<3 mmol/L) after unilateral surgical denervation. Para-aminohippurate (PAH) clearance, inulin, sodium excretion and arterio-venous blood glucose difference were measured every fifteen minutes. The statistical analysis was performed with a Wilcoxon signed-rank test. PAH, inulin, the calculated glomerular filtration rate and plasma flow did not change through renal denervation. Urinary sodium excretion increased significantly ( = 0.019). Side-dependent renal net glucose release (SGN) decreased by 25 ± 23% ( = 0.004). At 25 percent, the SGN decrease was only half of that observed in non-HPAA-altered animals in our prior investigation. The current findings may suggest that specimens with an elevated HPAA undergo long-term adaptations to maintain glucose homeostasis. Nonetheless, the decrease in SGN warrants further investigations and potentially caution in performing renal denervation in certain patient groups, such as diabetics at risk of hypoglycaemia.

摘要

先前,我们在猪模型中证实,肾脏去神经支配可使低血糖时的葡萄糖释放减少一半,而产前地塞米松注射会导致促肾上腺皮质激素 (ACTH) 和皮质醇浓度增加,作为低血糖时下丘脑-垂体-肾上腺轴 (HPAA) 活性增强的标志物。在这项研究中,我们研究了改变的 HPAA 对低血糖时肾脏葡萄糖释放的影响。对其母亲接受了两次晚期地塞米松注射的小猪进行单侧手术去神经支配后,进行 75 分钟的高胰岛素-低血糖钳夹 (<3 mmol/L)。每隔 15 分钟测量对氨基马尿酸 (PAH) 清除率、菊粉、钠排泄和动静脉血糖差。统计分析采用 Wilcoxon 符号秩检验。通过肾脏去神经支配,PAH、菊粉、计算肾小球滤过率和血浆流量没有变化。尿钠排泄显著增加(= 0.019)。肾脏净葡萄糖释放的侧依赖性 (SGN) 减少了 25 ± 23%(= 0.004)。在 25%时,SGN 的减少仅为我们之前的研究中未改变 HPAA 的动物的一半。目前的发现可能表明,具有升高的 HPAA 的标本经历了长期的适应以维持葡萄糖稳态。尽管如此,SGN 的减少需要进一步的研究,并可能需要在某些患者群体中谨慎进行肾脏去神经支配,例如有低血糖风险的糖尿病患者。

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