PRIMACY OF LIVER GLUCOSENSORS IN THE SYMPATHETIC RESPONSE TO PROGRESSIVE HYPOGLYCEMIA
PRIMACY OF LIVER GLUCOSENSORS IN THE SYMPATHETIC RESPONSE TO PROGRESSIVE HYPOGLYCEMIA
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DOI：
10.1073/pnas.91.7.2863
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发表时间：
1994-03-29
影响因子：
11.1
通讯作者：
BERGMAN, RN
中科院分区：
文献类型：
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作者：
DONOVAN, CM;HAMILTONWESSLER, M;BERGMAN, RN
在长期插管的清醒雄性狗（n = 6）中检查了肝葡萄糖浓度对进行性低血糖的交感神经反应的影响。通过外周胰岛素输注（30 pmol.kg-1.min-1）和外周（PER）或门脉（POR）葡萄糖输注诱导分级低血糖。在 260 分钟的实验期间，动脉血糖从 5.2 +/- 0.1 调整至 2.5 +/- 0.1 mM，每 40 分钟减少约 0.5 mM。在任何测量水平上，PER 和 POR 之间的动脉血糖没有显着差异。然而，与 PER（5.2 +/- 0.2 至 2.5 +/- 0.1 mM）相比，POR 期间的肝血糖始终显着升高（8.4 +/- 0.8 至 3.4 +/- 0.2 mM）。在所有动脉血糖低于 4.0 mM 的情况下，PER 期间的血浆肾上腺素值均显着高于 POR。在研究的最低动脉血糖水平 (2.5 +/- 0.2 mM) 下，与 POR (2.6 +/- 0.6 nM) 相比，PER (8.7 +/- 1.7 nM) 高于基础的肾上腺素反应是 POR (2.6 +/- 0.6 nM) 的 3 倍 (P < 0.01)。两种方案的血浆去甲肾上腺素结果相似，在 2.5 mM 动脉血糖条件下，与 POR 相比，PER 显示出比基础值高 3 倍的反应 (P < 0.05)。虽然当表达为动脉血糖的函数时，不同方案之间的交感神经反应明显不同，但当表达为肝血糖的函数时，这种差异基本上被消除了。后一项观察结果支持当低血糖缓慢发展（即在 2-3 小时内）时，肝脏是与交感肾上腺反应相关的血糖检测的主要场所。将当前研究结果与我们之前的观察结果进行比较表明，由于血糖下降速度较小，肝葡萄糖传感器可能在低血糖反调节中发挥更大作用。
The impact of hepatic glucose concentration on the sympathetic response to progressive hypoglycemia was examined in chronically cannulated conscious male dogs (n = 6). Graded hypoglycemia was induced via peripheral insulin infusion (30 pmol.kg-1.min-1) with either peripheral (PER) or portal (POR) glucose infusion. Over the 260-min experimental period, arterial glycemia was adjusted from 5.2 +/- 0.1 to 2.5 +/- 0.1 mM in decrements of almost-equal-to 0.5 mM every 40 min. Arterial glycemias were not significantly different between PER and POR at any measured level. However, hepatic glycemia was significantly elevated at all times during POR (8.4 +/- 0.8 to 3.4 +/- 0.2 mM) when compared to PER (5.2 +/- 0.2 to 2.5 +/- 0.1 mM). Plasma epinephrine values were significantly greater during PER vs. POR at all arterial glycemias below 4.0 mM. At the lowest level of arterial glycemia studied (2.5 +/- 0.2 mM) the epinephrine response above basal was 3-fold greater for PER (8.7 +/- 1.7 nM) when compared to POR (2.6 +/- 0.6 nM) (P < 0.01). Plasma norepinephrine results were similar for the two protocols, with PER demonstrating a 3-fold greater response above basal when compared to POR at 2.5 mM arterial glycemia (P < 0.05). While the sympathetic response was markedly different between protocols when expressed as a function of arterial glycemia, when expressed as a function of hepatic glycemia this discrepancy was largely eliminated. This latter observation supports the liver as the primary locus for glycemic detection relevant to the sympathoadrenal response when hypoglycemia develops slowly-i.e., over a period of 2-3 h. A comparison of the current findings with our previous observations suggests that the hepatic glucosensors may play a greater role in hypoglycemic counterregulation as the rate of fall in glycemia is less.