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GABA(A) 受体拮抗剂抑制剥夺诱导的摄食:下丘脑、内分泌和摄食机制的作用。

Inhibition of deprivation-induced food intake by GABA(A) antagonists: roles of the hypothalamic, endocrine and alimentary mechanisms.

机构信息

Department of Anesthesiology, University of Virginia Health Science System, Charlottesville, VA 22908, USA.

出版信息

J Clin Biochem Nutr. 2012 Jul;51(1):19-26. doi: 10.3164/jcbn.11-85. Epub 2012 Jun 8.

Abstract

The role of gamma amino butyric acid A receptors/neurons of the hypothalamic, endocrine and alimentary systems in the food intake seen in hunger was studied in 20 h food-deprived rats. Food deprivation decreased blood glucose, serum insulin and produced hyperphagia. The hyperphagia was inhibited by subcutaneous or ventromedial hypothalamic administration of gamma amino butyric acid A antagonists picrotoxin or bicuculline. Although results of blood glucose was variable, insulin level was increased by picrotoxin or bicuculline. In contrast, lateral hypothalamic administration of these agents failed to reproduce the above changes. Subcutaneous administration of picrotoxin or bicuculline increased gastric content, decreased gastric motility and small bowel transit. In contrast, ventromedial or lateral hypothalamic administration of picrotoxin or bicuculline failed to alter the gastric content but decreased the small bowel transit. The results of alimentary studies suggest that gamma amino butyric acid neurons of both ventromedial and lateral hypothalamus selectively regulate small bowel transit but not the gastric content. It may be concluded that ventromedial hypothalamus plays a dominant role in the regulation of food intake and that picrotoxin or bicuculline inhibited food intake by inhibiting gamma amino butyric acid receptors of the ventromedial hypothalamus, increasing insulin level and decreasing the gut motility.

摘要

研究了饥饿状态下下丘脑、内分泌和摄食系统的γ-氨基丁酸 A 受体/神经元在摄食中的作用,选用 20 小时禁食大鼠作为研究对象。禁食降低了血糖、血清胰岛素水平,导致摄食过度。γ-氨基丁酸 A 拮抗剂(如苦杏仁酸或印防己毒素)经皮下或腹内侧下丘脑给药可抑制摄食过度。尽管血糖水平变化不定,但苦杏仁酸或印防己毒素可增加胰岛素水平。相比之下,这些药物经外侧下丘脑给药则无法重现上述变化。皮下给予苦杏仁酸或印防己毒素可增加胃内容物,降低胃动力和小肠转运。相比之下,腹内侧或外侧下丘脑给予苦杏仁酸或印防己毒素则无法改变胃内容物,但可降低小肠转运。摄食研究结果表明,腹内侧和外侧下丘脑的γ-氨基丁酸神经元选择性调节小肠转运,而不影响胃内容物。可得出结论,腹内侧下丘脑在摄食调节中起主导作用,而苦杏仁酸或印防己毒素通过抑制腹内侧下丘脑的γ-氨基丁酸受体、增加胰岛素水平和降低肠道动力来抑制摄食。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb4/3391859/e4f8a8326c62/jcbn11-85f01.jpg

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