Meal-Anticipatory Glucagon-Like Peptide-1 Secretion in Rats

Meal-Anticipatory Glucagon-Like Peptide-1 Secretion in Rats
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DOI:
10.1210/en.2009-1002
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发表时间:
2010-02-01
期刊:
影响因子:
4.8
通讯作者:
Woods, Stephen C.
Woods, Stephen C.
中科院分区:
医学2区
文献类型:
--
作者:
Vahl, Torsten P.;Drazen, Deborah L.;Woods, Stephen C.

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期待进餐的动物会发起一系列反应,使它们能够更好地应对进餐的代谢影响。这些反应,例如头颅胰岛素,发生在摄入开始之前,并且在每天摄入食物有限但可预测的按膳食喂养计划的动物中尤其明显。我们测试了这样的假设:当进食的大鼠预计要吃大餐时,其头部会分泌肠促胰素激素胰高血糖素样肽-1 (GLP-1)。雄性 Long-Evans 大鼠随意喂养(对照)或适应每天相同 4 小时内可获得食物的时间表(膳食喂养动物)。喂食大鼠的血浆 GLP-1 在喂食前 75 至 60 分钟的时间内增加,从下午 10 点的基线增加到下午 40 点左右,然后在进食前恢复到基线。对照组在同一时间段内血浆 GLP-1 水平稳定(10-15 pM)。膳食喂养的大鼠也在食物呈现前 15 分钟左右开始分泌头部胰岛素。在 GLP-1 餐前峰值之前施用选择性 GLP-1 受体拮抗剂 exendin-4[desHis-1, Glu-9] 会导致餐食喂养的大鼠吃的食物明显少于正常情况,而在 GLP-1 峰值之后但在食物呈现之前施用拮抗剂会导致食物消耗量显着增加。这些发现首次记录了血浆 GLP-1 的头侧增加,并表明它有助于促进大餐的消耗。 (内分泌学 151:569-575,2010)
Animals anticipating a meal initiate a series of responses enabling them to better cope with the meal's metabolic impact. These responses, such as cephalic insulin, occur prior to the onset of ingestion and are especially evident in animals maintained on a meal-feeding schedule with limited but predictable access to food each day. We tested the hypothesis that meal-fed rats secrete the incretin hormone glucagon-like peptide-1 (GLP-1) cephalically when anticipating a large meal. Male Long-Evans rats were fed ad libitum (controls) or adapted to a schedule on which food was available for the same 4-h period each day (meal fed animals). Plasma GLP-1 increased in meal-fed rats over an interval from 75 to 60 min prior to feeding time, from a baseline of 10 to around 40 pM, and then returned to baseline prior to food presentation. Controls had steady plasma GLP-1 levels (10-15 pM) over the same span. Meal-fed rats also secreted cephalic insulin starting around 15 min prior to food presentation. Administration of the selective GLP-1 receptor antagonist exendin-4[desHis-1, Glu-9] prior to the premeal spike of GLP-1 caused meal-fed rats to eat significantly less food than normal, whereas administration of the antagonist after the GLP-1 spike but prior to food presentation resulted in a significant increase in food consumption. These findings document for the first time a cephalic increase of plasma GLP-1 and suggest that it functions to facilitate consumption of a large meal. (Endocrinology 151: 569-575, 2010)