Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding.
Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding.
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DOI：
10.1523/jneurosci.0334-09.2009
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发表时间：
2009-05-27
期刊：
影响因子：
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通讯作者：
Levin BE
中科院分区：
文献类型：
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作者：
Dunn-Meynell AA;Sanders NM;Compton D;Becker TC;Eiki J;Zhang BB;Levin BE
尽管一些研究暗示血糖水平的小幅下降是自发进食的刺激，但这些下降如何启动进食的机制尚不清楚。为了评估腹内侧下丘脑（VMH;弓状核+腹内侧核）葡萄糖敏感神经元作为自发和葡萄糖缺乏性进食的潜在介质的作用，观察评估15只大鼠的膳食模式，并在黑暗开始后3.5小时和胰岛素（5 U/kg，i. v.）输液在65%的自发进餐前约5分钟开始，血糖水平下降11%，VMH水平没有下降。在胰岛素后，血液和VMH葡萄糖在30-40分钟达到最低点，相同的大鼠在随后的低血糖期间进食速度加快60%，进食时间增加84%。尽管83%的第一次低血糖餐之前VMH（而不是血液）葡萄糖水平下降5分钟，但在第二次餐之前血液和VMH水平都没有下降，这表明低葡萄糖而不是改变水平是葡萄糖缺乏餐的刺激。此外，通过提高或降低葡萄糖激酶（GK）活性来改变VMH葡萄糖传感未能影响自发摄食、体重或脂肪重量或葡萄糖耐量。另一方面，VMH GK mRNA的26-70%的慢性消耗减少了葡萄糖消耗。因此，虽然VMH葡萄糖传感似乎不参与自发摄食或长期体重调节，但它确实参与葡萄糖缺乏摄食，类似于其在葡萄糖缺乏的反调节神经体液反应中的作用。
Although several studies implicate small declines in blood glucose levels as stimulus for spontaneous meal initiation, no mechanism is known for how these dips might initiate feeding. To assess the role of ventromedial hypothalamus (VMH; arcuate + ventromedial nucleus) glucosensing neurons as potential mediators of spontaneous and glucoprivic feeding, meal patterns were observed evaluated and blood and VMH microdialysis fluid were sampled in 15 rats every 10 min for 3.5 h after dark onset and 2 h after insulin (5 U/kg, i.v.) infusion. Blood glucose levels declined by 11% beginning ~5 min prior to 65% of all spontaneous meals, with no fall in VMH levels. Following insulin, blood and VMH glucose reached nadirs by 30–40 min and the same rats ate 60% faster and spent 84% more time eating during the ensuing hypoglycemia. Although 83% of first hypoglycemic meals were preceded by 5 min dips in VMH (but not blood) glucose levels, neither blood nor VMH levels declined prior to second meals suggesting that low glucose, rather than changing levels was the stimulus for glucoprivic meals. Furthermore, altering VMH glucosensing by raising or lowering glucokinase (GK) activity failed to affect spontaneous feeding, body or adipose weights or glucose tolerance. On the other hand, chronic depletion by 26–70% of VMH GK mRNA reduced glucoprivic feeding. Thus, while VMH glucosensing does not appear be involved in either spontaneous feeding or long-term body weight regulation, it does participate in glucoprivic feeding, similar to its role in the counterregulatory neurohumoral responses to glucoprivation.