Pfeifer M A, Beard J C, Halter J B, Judzewitsch R, Best J D, Porte D
J Clin Endocrinol Metab. 1983 Mar;56(3):586-91. doi: 10.1210/jcem-56-3-586.
To determine the effect of tolbutamide on glucagon release in noninsulin-dependent diabetic and normal subjects and how plasma glucose levels may modulate this effect, the acute glucagon response (AGR) to a 5-g iv arginine pulse was determined before and during a tolbutamide infusion. There was a decrease in plasma glucose concentration in both normal and diabetic subjects (both P less than 0.001); there tended to be a suppression of the AGR (4 of 6 normals and 8 of 11 diabetics), but this suppression was not statistically significant. In separate studies, when the plasma glucose level was clamped at baseline values by a variable rate of glucose infusion, the AGR was suppressed during the tolbutamide infusion in all 7 normal [change in AGR (delta AGR) = -35 +/- 12 pg/ml; P less than 0.05] and all 6 noninsulin-dependent diabetic subjects (delta AGR = -14 +/- 5 pg/ml, p less than .05). In 6 insulin-dependent diabetic subjects, there was no evidence of glucagon suppression by tolbutamide (delta AGR = +2 +/- 2 pg/ml). These results are consistent with the hypothesis that sulfonylureas suppress glucagon secretion by augmenting insulin secretion, an effect that falling glucose levels can mask. Consideration of this observation is necessary when interpreting the effects of a sulfonylurea on islet cell responses.
为了确定甲苯磺丁脲对非胰岛素依赖型糖尿病患者和正常受试者胰高血糖素释放的影响，以及血糖水平如何调节这种影响，在输注甲苯磺丁脲之前和期间，测定了对5g静脉注射精氨酸脉冲的急性胰高血糖素反应（AGR）。正常受试者和糖尿病患者的血糖浓度均降低（均P<0.001）；AGR有被抑制的趋势（6名正常受试者中的4名和11名糖尿病患者中的8名），但这种抑制无统计学意义。在另外的研究中，当通过可变速率的葡萄糖输注将血糖水平维持在基线值时，在所有7名正常受试者（AGR变化量（ΔAGR）=-35±12 pg/ml；P<0.05）和所有6名非胰岛素依赖型糖尿病受试者（ΔAGR=-14±5 pg/ml，P<0.05）中，甲苯磺丁脲输注期间AGR受到抑制。在6名胰岛素依赖型糖尿病受试者中，没有证据表明甲苯磺丁脲可抑制胰高血糖素（ΔAGR=+2±2 pg/ml）。这些结果与以下假设一致，即磺脲类药物通过增强胰岛素分泌来抑制胰高血糖素分泌，而血糖水平下降可能掩盖这一效应。在解释磺脲类药物对胰岛细胞反应的影响时，有必要考虑这一观察结果。
