Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamus nucleus
Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamus nucleus
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DOI：
10.1152/ajpregu.00148.2006
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发表时间：
2006-11-01
影响因子：
2.8
通讯作者：
Routh, Vanessa H.
中科院分区：
文献类型：
--
作者：
Song, Zhentao;Routh, Vanessa H.
反复发作的低血糖会削弱大脑感知和应对后续低血糖发作的能力。下丘脑腹内侧核（VMN）中的葡萄糖敏感神经元在低血糖检测中发挥作用。VMN葡萄糖抑制（GI）神经元，其放电率随着细胞外葡萄糖的增加而降低，对细胞外葡萄糖的减少非常敏感。我们推测，反复低血糖降低VMN GI神经元的葡萄糖敏感性。为了验证我们的假设，连续三天皮下注射14至21日龄的Sprague-Dawley大鼠常规人胰岛素（4 U/kg）或生理盐水（对照）。第3天胰岛素注射后1小时的血糖水平显著低于第1天，反映了抵抗低血糖的能力受损。第4天，使用传统的全细胞电流钳记录测量VMN GI神经元的葡萄糖敏感性。反复胰岛素诱导的低血糖后，VMN GI神经元仅对葡萄糖从2.5降至0.1作出反应，但不对0.5 mM作出反应。此外，补充乳酸也降低了VMN GI神经元的葡萄糖敏感性。因此，我们的研究结果表明，葡萄糖敏感性的VMN GI神经元的降低可能有助于在中枢葡萄糖敏感机制的损害后，反复低血糖。
Recurrent hypoglycemia blunts the brain's ability to sense and respond to subsequent hypoglycemic episodes. Glucose-sensing neurons in the ventromedial hypothalamus nucleus (VMN) are well situated to play a role in hypoglycemia detection. VMN glucose-inhibited (GI) neurons, which decrease their firing rate as extracellular glucose increases, are extremely sensitive to decreased extracellular glucose. We hypothesize that recurrent hypoglycemia decreases the glucose sensitivity of VMN GI neurons. To test our hypothesis, 14- to 21-day-old Sprague-Dawley rats were subcutaneously injected with regular human insulin (4 U/kg) or saline (control) for three consecutive days. Blood glucose levels 1 h after insulin injection on day 3 were significantly lower than on day 1, reflecting an impaired ability to counteract hypoglycemia. On day 4, the glucose sensitivity of VMN GI neurons was measured using conventional whole cell current-clamp recording. After recurrent insulin-induced hypoglycemia, VMN GI neurons only responded to a glucose decrease from 2.5 to 0.1, but not 0.5, mM. Additionally, lactate supplementation also decreased glucose sensitivity of VMN GI neurons. Thus our findings suggest that decreases in glucose sensitivity of VMN GI neurons may contribute to the impairments in central glucose-sensing mechanisms after recurrent hypoglycemia.