Adaptation of Feeding and Counter-Regulatory Hormone Responses to Intermediate Insulin-Induced Hypoglycaemia in the Ovariectomised Female Rat: Effects of Oestradiol
Adaptation of Feeding and Counter-Regulatory Hormone Responses to Intermediate Insulin-Induced Hypoglycaemia in the Ovariectomised Female Rat: Effects of Oestradiol
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DOI：
10.1111/j.1365-2826.2009.01872.x
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发表时间：
2009-06-01
影响因子：
3.2
通讯作者：
Nedungadi, T. P.
中科院分区：
文献类型：
--
作者：
Briski, K. P.;Nedungadi, T. P.
雌二醇调节基础食物摄入量以及高血糖素和皮质酮的分泌，但其对急性和复发性低血糖反应的影响尚不清楚。本研究利用了一种重复的中效胰岛素诱导低血糖的实验模型，该模型复制了临床环境中胰岛素的给药途径、给药频率和持续时间。卵巢切除(OVX)组大鼠植入皮下SC。含有苯甲酸雌二醇酯(EB)或油的胶囊，并注射一剂或四剂葫芦素中性鱼精蛋白(HN)，连续几天注射，或仅注射稀释剂。在最后一次注射后的9小时内，基线喂养遵循了EB和油植入动物的不同趋势。与急性低血糖高吞噬相比，OVX+EB组和OVX+油组反复出现的HN诱导的低血糖导致基线校正后的食物摄入量显著增加。虽然雌二醇在单次或连续服用HN后没有改变净食物消耗量，但EB替代在每种治疗范例中都保持了随时间的均匀进食。EB-OVX组大鼠的基线高血糖素和皮质酮分泌高于油处理组大鼠。雌二醇可延长急性低血糖血症，并在反复低血糖期间增加高血糖素分泌的幅度，但缩短持续时间。OVX+OIL大鼠对急性低血糖和复发性低血糖均有反应，皮质酮分泌在单个时间点升高，在胰岛素诱导的复发性低血糖期间，皮质酮分泌从+6h提前到+4h，而OVX+EB大鼠在+4h和+6h均表现出血浆激素水平的升高。曲线下面积分析表明，单次和连续给药HN后，EB植入的大鼠的总胰高血糖素和皮质酮的释放比石油植入的大鼠更大。这些结果表明，重复给予HN通过雌激素非依赖性机制增加雌性大鼠的摄食量，但雌二醇保留了低血糖高吞噬的时间模式。数据还显示，在雌激素存在的情况下，正常和低血糖的胰高血糖素和皮质酮的分泌都会增加。需要进一步的研究来确定对长期低血糖的行为和内分泌反应的荷尔蒙调节负责的部位和细胞底物。
Oestradiol regulates basal food intake and glucagon and corticosterone secretion, but its influence on these responses to acute and recurring hypoglycaemia remains unclear. The present study utilised an experimental model for repeated intermediate-acting insulin-induced hypoglycaemia that replicates the route of delivery, frequency of administration, and duration of insulin action in the clinical setting. Groups of ovariectomised (OVX) rats were implanted with s.c. capsules containing oestradiol benzoate (EB) or oil, and injected with one or four doses of Humulin neutral protamine Hagedorn (HN), on as many days, or diluent alone. Baseline feeding followed divergent trends in EB- versus oil-implanted animals over a 9-h period after final injections. Recurring HN-induced hypoglycaemia resulted in significantly greater baseline-corrected food intake in OVX + EB and OVX + oil groups, relative to acute hypoglycaemic hyperphagia. Although oestradiol did not modify net food consumption after single or serial HN doses, EB replacement maintained uniform feeding over time in each treatment paradigm. Baseline glucagon and corticosterone secretion was higher in EB- versus oil-treated OVX rats. Oestradiol prolonged acute hypoglycaemic glucagonemia, and increased the magnitude, but shortened the duration, of glucagon secretion during recurring hypoglycaemia. OVX + oil rats responded to both acute and recurring hypoglycaemia with elevated corticosterone secretion at a single time point, which was advanced from +6 to +4 h during recurrent insulin-induced hypoglycemia, whereas OVX + EB animals exhibited increased plasma hormone levels at both +4 and +6 h in response to each paradigm. Area-under-the curve analyses showed that total glucagon and corticosterone release was greater in EB- versus oil-implanted rats after both single and serial dosing with HN. These results demonstrate that repeated HN administration increases food intake in female rats via oestrogen-independent mechanisms, but that oestradiol preserves temporal patterns of hypoglycaemic hyperphagia. The data also reveal that normo- and hypoglyacemic glucagon and corticosterone secretion are enhanced in the presence of oestrogen. Further studies are necessary to identify the sites and cellular substrates that are responsible for this hormonal regulation of behavioural and endocrine responses to prolonged hypoglycaemia.