Recurrent hypoglycemia impairs hormonal counterregulatory responses (CRRs) to further bouts of hypoglycemia. The hypothalamus and hindbrain are both critical for sensing hypoglycemia and triggering CRRs. Hypothalamic glucose sensing sites are implicated in the pathogenesis of defective CRRs; however, the contribution of hindbrain glucose sensing has not been elucidated. Using a rat model, we compared the effect of antecedent glucoprivation targeting hindbrain or hypothalamic glucose sensing sites with the effect of antecedent recurrent hypoglycemia on CRR to hypoglycemia induced 24 h later. Recurrent hypoglycemia decreased sympathoadrenal (1,470 ± 325 vs. 3,811 ± 540 pg/ml in controls [t = 60 min], P = 0.001) and glucagon secretion (222 ± 43 vs. 494 ± 56 pg/ml in controls [t = 60]), P = 0.003) in response to hypoglycemia. Antecedent 5-thio-glucose (5TG) injected into the hindbrain did not impair sympathoadrenal (3,806 ± 344 pg/ml [t = 60]) or glucagon (513 ± 56 pg/ml [t = 60]) responses to subsequent hypoglycemia. However, antecedent 5TG delivered into the third ventricle was sufficient to blunt CRRs to hypoglycemia. These results show that hindbrain glucose sensing is not involved in the development of defective CRRs. However, neural substrates surrounding the third ventricle are particularly sensitive to glucoprivic stimulation and may contribute importantly to the development of defective CRRs.
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机译：反复出现的低血糖会损害对进一步降低血糖的激素反调节反应（CRR）。下丘脑和后脑对于感知低血糖和触发CRR均至关重要。下丘脑葡萄糖感测位点与CRR缺陷的发病机制有关。但是，后脑葡萄糖感测的作用尚未阐明。使用大鼠模型，我们比较了针对后脑或下丘脑葡萄糖感应部位的前期葡萄糖缺乏与前期反复低血糖对CRR和24小时后诱发的低血糖的影响的比较。复发性低血糖会降低交感肾上腺（对照组为1,470±325 vs. 3,811±540 pg / ml [t = 60分钟]，P = 0.001）和胰高血糖素分泌（对照组为222±43 vs. 494±56 pg / ml [t = 60 ]），P = 0.003）应对低血糖症。前脑中注入的5-硫代葡萄糖（5TG）不会损害对随后低血糖的交感肾上腺（3,806±344 pg / ml [t = 60]）或胰高血糖素（513±56 pg / ml [t = 60]）的反应。然而，先天进入第三脑室的5TG足以使CRR减弱为低血糖。这些结果表明后脑葡萄糖感测不参与有缺陷的CRR的发展。但是，第三脑室周围的神经底物对糖皮质激素刺激特别敏感，并且可能对缺陷性CRR的发展起重要作用。
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