Silva G, Gomis R, Bosch J, Casamitjana R, Mastai R, Navasa M, Rivera F, Rodés J
Liver Unit, Hospital Clinic i Provincial, University of Barcelona, School of Medicine, Spain.
J Hepatol. 1988 Jun;6(3):325-31. doi: 10.1016/s0168-8278(88)80049-7.
Propranolol, a non-selective beta-blocker, is known to decrease glucagon release in normal subjects. The present study was aimed at investigating the effects of propranolol on the hyperglucagonism commonly observed in patients with cirrhosis. Eight cirrhotic patients and 6 matched healthy controls were studied. The plasma concentrations of glucagon, insulin, c-peptide and glucose were measured in basal conditions and after stimulating glucagon secretion by an i.v. infusion of arginine (0.4 g/kg/30 min). The study was repeated 24 h later after inducing beta-blockade by the i.v. infusion of propranolol (10 mg). In baseline conditions, patients with cirrhosis, despite normal levels of insulin and glucose, had a marked hyperglucagonism (654 +/- 303 pg/ml vs. 269 +/- 90 in controls, P less than 0.01). Prior to propranolol, arginine infusion caused greater glucagon release in cirrhotics (71 +/- 31 ng.h.ml-1) than in controls (33 +/- 17 ng.h.ml-1, P less than 0.02), but despite a similar insulin secretion (assessed from c-peptide), blood glucose did not increase. After propranolol, glucagon secretion decreased as expected in controls (29 +/- 12 ng.h.ml-1, P less than 0.05) but experienced a paradoxical increase in cirrhotics (113 +/- 64 ng.h.ml-1, P less than 0.05). Again, despite the marked increase in glucagon release, there was no increase in glucose production, providing further evidence of the glucagon resistance that accompanies hyperglucagonism in cirrhosis. Our results suggest that hyperglucagonism with glucagon resistance might be the initial disturbance in carbohydrate metabolism in patients with cirrhosis. Contrary to what could be expected, propranolol does not correct but further accentuates this disturbance.
普萘洛尔是一种非选择性β受体阻滞剂，已知它可降低正常受试者体内胰高血糖素的释放。本研究旨在调查普萘洛尔对肝硬化患者中常见的高胰高血糖素血症的影响。研究了8名肝硬化患者和6名匹配的健康对照者。在基础状态下以及通过静脉输注精氨酸（0.4 g/kg/30分钟）刺激胰高血糖素分泌后，测量了血浆中胰高血糖素、胰岛素、C肽和葡萄糖的浓度。在静脉输注普萘洛尔（10 mg）诱导β受体阻滞24小时后，重复进行该研究。在基线状态下，肝硬化患者尽管胰岛素和葡萄糖水平正常，但存在明显的高胰高血糖素血症（654±303 pg/ml，而对照组为269±90 pg/ml，P<0.01）。在使用普萘洛尔之前，精氨酸输注导致肝硬化患者的胰高血糖素释放量（71±31 ng·h·ml⁻¹）高于对照组（33±17 ng·h·ml⁻¹，P<0.02），但尽管胰岛素分泌相似（根据C肽评估），血糖并未升高。使用普萘洛尔后，对照组的胰高血糖素分泌如预期般减少（29±12 ng·h·ml⁻¹，P<0.05），但肝硬化患者却出现了反常的增加（113±64 ng·h·ml⁻¹，P<0.05）。同样，尽管胰高血糖素释放量显著增加，但葡萄糖生成并未增加，这进一步证明了肝硬化患者高胰高血糖素血症伴随的胰高血糖素抵抗。我们的结果表明，伴有胰高血糖素抵抗的高胰高血糖素血症可能是肝硬化患者碳水化合物代谢的初始紊乱。与预期相反，普萘洛尔并不能纠正反而进一步加重了这种紊乱。
