Sirek O V, Sirek Z, Policova Z
Diabetologia. 1975 Aug;11(4):269-72. doi: 10.1007/BF00422390.
Normal dogs were injected i.v. with a single dose of 0.25 mg/kg sodium salt of HB 419 (Glibenclamide). Plasma insulin and glucose concentrations were measured at stated intervals over a period of two hours. The rise in insulin, but not the hypoglycemic response was abolished in peripheral blood when the animals were pretreated with a single i.v. injection of either 0.1 mg/kg or 0.3 mg/kg dl-propranolol, 30 min prior to the administration of HB 419. The d-isomer of propranolol was ineffective in this respect. These results indicate that a) the mechanism by which propranolol inhibits sulphonylurea-stimulated insulin secretion involves beta adrenergic receptors; and b) the hypoglycemia produced by HB 419 in the presence of propranolol could be the result of extrapancreatic effects. Since the possibility of an early rise in the insulin concentration of portal blood was not excluded in our present series of experiments, final proof will have to be provided by studies in totally pancreatectomized dogs.
给正常犬静脉注射单剂量0.25mg/kg的HB 419（格列本脲）钠盐。在两小时内按规定间隔测量血浆胰岛素和葡萄糖浓度。当动物在注射HB 419前30分钟预先静脉注射0.1mg/kg或0.3mg/kg的dl-普萘洛尔时，外周血中胰岛素的升高，但低血糖反应未被消除。普萘洛尔的d-异构体在这方面无效。这些结果表明：a）普萘洛尔抑制磺酰脲刺激的胰岛素分泌的机制涉及β肾上腺素能受体；b）在普萘洛尔存在下HB 419产生的低血糖可能是胰腺外效应的结果。由于在我们目前的一系列实验中未排除门静脉血胰岛素浓度早期升高的可能性，最终证据必须由全胰切除犬的研究提供。
