Chu C A, Sindelar D K, Igawa K, Sherck S, Neal D W, Emshwiller M, Cherrington A D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E463-73. doi: 10.1152/ajpendo.2000.279.2.E463.
The role of alpha- and beta-adrenergic receptor subtypes in mediating the actions of catecholamines on hepatic glucose production (HGP) was determined in sixteen 18-h-fasted conscious dogs maintained on a pancreatic clamp with basal insulin and glucagon. The experiment consisted of a 100-min equilibration, a 40-min basal, and two 90-min test periods in groups 1 and 2, plus a 60-min third test period in groups 3 and 4. In group 1 [alpha-blockade with norepinephrine (alpha-blo+NE)], phentolamine (2 microg x kg(-1) x min(-1)) was infused portally during both test periods, and NE (50 ng x kg(-1) x min(-1)) was infused portally at the start of test period 2. In group 2, beta-blockade with epinephrine (beta-blo+EPI), propranolol (1 microg x kg(-1) x min(-1)) was infused portally during both test periods, and EPI (8 ng x kg(-1) x min(-1)) was infused portally during test period 2. In group 3 (alpha(1)-blo+NE), prazosin (4 microg x kg(-1) x min(-1)) was infused portally during all test periods, and NE (50 and 100 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In group 4 (beta(2)-blo+EPI), butoxamine (40 microg x kg(-1) x min(-1)) was infused portally during all test periods, and EPI (8 and 40 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In the presence of alpha- or alpha(1)-adrenergic blockade, a selective rise in hepatic sinusoidal NE failed to increase net hepatic glucose output (NHGO). In a previous study, the same rate of portal NE infusion had increased NHGO by 1.6 +/- 0.3 mg x kg(-1) x min(-1). In the presence of beta- or beta(2)-adrenergic blockade, the selective rise in hepatic sinusoidal EPI caused by EPI infusion at 8 ng x kg(-1) x min(-1) also failed to increase NHGO. In a previous study, the same rate of EPI infusion had increased NHGO by 1.6 +/- 0.4 mg x kg(-1) x min(-1). In conclusion, in the conscious dog, the direct effects of NE and EPI on HGP are predominantly mediated through alpha(1)- and beta(2)-adrenergic receptors, respectively.
在16只禁食18小时的清醒犬中，通过胰腺钳夹维持基础胰岛素和胰高血糖素水平，以确定α和β肾上腺素能受体亚型在介导儿茶酚胺对肝葡萄糖生成（HGP）作用中的角色。实验包括100分钟的平衡期、40分钟的基础期，第1组和第2组有两个90分钟的测试期，第3组和第4组还有一个60分钟的第三个测试期。在第1组[用去甲肾上腺素进行α受体阻断（α - blo + NE）]中，在两个测试期均经门静脉输注酚妥拉明（2微克·千克⁻¹·分钟⁻¹），并在测试期2开始时经门静脉输注去甲肾上腺素（50纳克·千克⁻¹·分钟⁻¹）。在第2组，用肾上腺素进行β受体阻断（β - blo + EPI），在两个测试期均经门静脉输注普萘洛尔（1微克·千克⁻¹·分钟⁻¹），并在测试期2经门静脉输注肾上腺素（8纳克·千克⁻¹·分钟⁻¹）。在第3组（α₁ - blo + NE）中，在所有测试期均经门静脉输注哌唑嗪（4微克·千克⁻¹·分钟⁻¹），并在测试期2和3分别经门静脉输注去甲肾上腺素（50和100纳克·千克⁻¹·分钟⁻¹）。在第4组（β₂ - blo + EPI）中，在所有测试期均经门静脉输注丁氧胺（40微克·千克⁻¹·分钟⁻¹），并在测试期2和3分别经门静脉输注肾上腺素（8和40纳克·千克⁻¹·分钟⁻¹）。在存在α或α₁肾上腺素能阻断的情况下，肝窦去甲肾上腺素选择性升高未能增加肝脏净葡萄糖输出（NHGO）。在先前的一项研究中，相同速率的门静脉去甲肾上腺素输注使NHGO增加了1.6±0.3毫克·千克⁻¹·分钟⁻¹。在存在β或β₂肾上腺素能阻断时，由以8纳克·千克⁻¹·分钟⁻¹速率输注肾上腺素引起的肝窦肾上腺素选择性升高也未能增加NHGO。在先前的一项研究中，相同速率肾上腺素输注使NHGO增加了1.6±0.4毫克·千克⁻¹·分钟⁻¹。总之，在清醒犬中，去甲肾上腺素和肾上腺素对HGP的直接作用分别主要通过α₁和β₂肾上腺素能受体介导。
