Wiethop B V, Cryer P E
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Diabetes Care. 1993 Aug;16(8):1131-6. doi: 10.2337/diacare.16.8.1131.
To test the hypothesis that, in contrast to administration of glucose or glucagon, administration of the amino acid Ala or of the beta 2-adrenergic agonist terbutaline produces sustained glucose recovery from hypoglycemia.
We developed a model of clinical hypoglycemia using subcutaneous injection of insulin (0.15 U/kg) in patients with IDDM. In comparison with nondiabetic subjects, patients with IDDM exhibited reduced glucagon (P = 0.0001), epinephrine (P = 0.0060), and pancreatic polypeptide (P = 0.0001) responses to hypoglycemia. In addition to placebos, the following were administered during hypoglycemia (2 h after insulin injection) in IDDM patients: oral glucose, 10 and 20 g; subcutaneous glucagon, 1.0 mg; oral Ala, 40 g; oral terbutaline, 5.0 mg; and subcutaneous terbutaline, 0.25 mg.
Glucose (10 and 20 g) and glucagon raised plasma glucose (P = 0.0163, 0.0060, and 0.0001, respectively) from 3.0-3.3 mM to peaks of 5.4 +/- 0.4, 6.8 +/- 0.7, and 11.8 +/- 0.8 mM within 30, 45, and 60 min, respectively, but the responses were transient. Oral Ala raised glucose levels (P = 0.0401) to 4.0 +/- 0.4 mM within 30 min; glucose levels then rose gradually to a 6-h value of only 7.1 +/- 0.9 mM. Oral terbutaline raised glucose levels (P = 0.0294) to 4.3 +/- 0.3 mM within 30 min; glucose levels then rose substantially. In contrast, subcutaneous terbutaline raised glucose levels (P = 0.0249) to 3.7 +/- 0.1 mM within 15 min; the levels plateaued at 5.0 mM from approximately 60-150 min and then paralleled the placebo curve.
Ala and terbutaline produce sustained glucose recovery from hypoglycemia in IDDM and are therefore potentially useful agents for the treatment of mild or moderate iatrogenic hypoglycemia, or the prevention of iatrogenic hypoglycemia, when food intake is not anticipated over the following several hours.
验证以下假说：与给予葡萄糖或胰高血糖素相比，给予氨基酸丙氨酸（Ala）或β2肾上腺素能激动剂特布他林可使低血糖状态下的血糖持续恢复。
我们通过给胰岛素依赖型糖尿病（IDDM）患者皮下注射胰岛素（0.15 U/kg）建立了临床低血糖模型。与非糖尿病受试者相比，IDDM患者对低血糖的胰高血糖素（P = 0.0001）、肾上腺素（P = 0.0060）和胰多肽（P = 0.0001）反应降低。在IDDM患者低血糖期间（胰岛素注射后2小时），除给予安慰剂外，还给予以下物质：口服葡萄糖，10克和20克；皮下注射胰高血糖素，1.0毫克；口服Ala，40克；口服特布他林，5.0毫克；皮下注射特布他林，0.25毫克。
葡萄糖（10克和20克）和胰高血糖素分别在30、45和60分钟内使血浆葡萄糖从3.0 - 3.3毫摩尔升至峰值5.4±0.4、6.8±0.7和11.8±0.8毫摩尔（P分别为0.0163、0.0060和0.0001），但反应是短暂的。口服Ala在30分钟内使血糖水平升至4.0±0.4毫摩尔（P = 0.0401）；随后血糖水平逐渐上升，6小时时仅为7.1±0.9毫摩尔。口服特布他林在30分钟内使血糖水平升至4.3±0.3毫摩尔（P = 0.0294）；随后血糖水平大幅上升。相比之下，皮下注射特布他林在15分钟内使血糖水平升至3.7±0.1毫摩尔（P = 0.0249）；在约60 - 150分钟内血糖水平稳定在约5.0毫摩尔，然后与安慰剂曲线平行。
Ala和特布他林可使IDDM患者低血糖状态下的血糖持续恢复，因此在接下来数小时内预计无法进食时，可能是治疗轻度或中度医源性低血糖或预防医源性低血糖的有效药物。
