Glucocorticoids upregulate intestinal nutrient transport in a time-dependent and substrate-specific fashion.

Glucocorticoids upregulate intestinal nutrient transport in a time-dependent and substrate-specific fashion.
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DOI:
10.1016/s1091-255x(98)80036-x
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发表时间:
1998-09-01
期刊:
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
影响因子:
--
通讯作者:
Sax, H C
Sax, H C
中科院分区:
其他
文献类型:
--
作者:
Iannoli, P;Miller, J H;Sax, H C

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糖皮质激素介导危重病期间骨骼肌蛋白水解,为肝脏急性期蛋白合成和肝脏异生提供底物。高皮质醇血症对内脏基质摄取的影响尚未明确。这项研究的特点是肠道营养转运的血浆糖皮质激素水平急性升高的反应。新西兰白色家兔随机接受地塞米松(2 mg/kg肌内注射)或溶剂,并在类固醇治疗后8、16或24小时处死。从合并的小肠粘膜制备刷状缘膜囊泡,并定量氚化底物的摄取。测定血清胰岛素样生长因子1(IGF-1)水平、粘膜DNA含量和粘膜形态。糖皮质激素在8小时(分别为80%和24%)和24小时(分别为147%和50%)增加葡萄糖和亮氨酸摄取。谷氨酰胺、丙氨酸和精氨酸转运在24小时时分别增加42%、96%和236%。地塞米松处理24小时后,所有底物的钠非依赖性转运(扩散)增加240%。在24小时,粘液DNA含量增加了32%,而微绒毛高度降低了27%。未观察到对IGF-1水平或总绒毛高度的影响。糖皮质激素以时间相关和底物特异性方式急剧加速肠道营养转运。虽然糖皮质激素的作用机制尚不清楚,但基因组和质膜效应都有牵连。
Glucocorticoids mediate skeletal muscle proteolysis during critical illness to provide substrates for hepatic acute-phase protein synthesis and gluconeogenesis. The effects of hypercortisolemia on splanchnic substrate uptake are not well defined. This study characterizes intestinal nutrient transport in response to acute elevations of plasma glucocorticoid levels. New Zealand White rabbits were randomized to receive either dexamethasone (2 mg/kg intramuscularly) or vehicle and were killed 8, 16, or 24 hours after steroid treatment. Brush-border membrane vesicles were prepared from pooled small intestinal mucosa and the uptake of tritiated substrates was quantified. Serum insulin-like growth factor 1 (IGF-1) levels, mucosal DNA content, and mucosal morphology were determined. Glucocorticoids increased glucose and leucine uptake at 8 hours (80% and 24%, respectively) and 24 hours (147% and 50%, respectively). Glutanmine, alanine, and arginine transport increased by 42%, 96%, and 236%, respectively, at 24 hours. Sodium-independent transport (diffusion) of all substrates was increased by 240% by dexamethasone treatment at 24 hours. Mucosal DNA content increased by 32%, whereas microvillus heights decreased by 27% at 24 hours. No effects were noted on IGF-1 levels or gross villus heights. Glucocorticoids acutely accelerate intestinal nutrient transport in a time-related and substrate-specific fashion. Although the mechanism of glucocorticoid action remains unclear, both genomic and plasma membrane effects are implicated.