Tötterman K, Groop L, Groop P H, Kala R, Tolppanen E M, Fyhrquist F
Eur J Clin Pharmacol. 1984;26(1):13-7. doi: 10.1007/BF00546701.
The effects of two beta-blocking drugs on endogenous insulin secretion and insulin sensitivity were investigated in a double-blind cross-over study in 13 hypertensive patients. The patients were randomly allocated to each of three 2-week treatment periods with propranolol 80 mg b.i.d., atenolol 50 mg b.i.d. and placebo b.i.d. Endogenous insulin secretion was assessed by measuring serum insulin and C-peptide before and 6 min after iv administration of glucagon; insulin sensitivity was determined by measuring insulin binding to erythrocytes, and as the glucose disappearance rate (KITT) after i.v. insulin. Fasting concentrations of serum free fatty acids (S-FFA) and plasma gastric inhibitory polypeptide (P-GIP) were also recorded during the three study periods. Both propranolol and atenolol reduced blood pressure, heart rate and S-FFA concentrations compared to placebo, and all patients showed measurable plasma concentrations of propranolol and atenolol. The results can be considered representative, therefore, of clinical beta-blockade. The two drugs did not significantly influence the fasting blood glucose level. There was an increase in fasting and glucagon-stimulated serum C-peptide concentration during propranolol therapy compared with placebo (p = 0.037 and p = 0.030, respectively), although this was not reflected by a significant change in serum insulin. Propranolol and atenolol did not significantly influence insulin binding to erythrocytes, but they clearly reduced the glucose disappearance rate KITT was compared to placebo (p = 0.0036 and p = 0.0003), respectively). The findings support the view that beta-blocking drugs can influence glucose metabolism by mechanisms other than inhibition of endogenous insulin secretion.
在一项针对13名高血压患者的双盲交叉研究中，研究了两种β受体阻滞剂对内源性胰岛素分泌和胰岛素敏感性的影响。患者被随机分配到三个为期2周的治疗阶段，分别接受每日两次80毫克普萘洛尔、每日两次50毫克阿替洛尔和每日两次安慰剂治疗。通过静脉注射胰高血糖素前及注射后6分钟测量血清胰岛素和C肽来评估内源性胰岛素分泌；通过测量胰岛素与红细胞的结合以及静脉注射胰岛素后的葡萄糖消失率（KITT）来确定胰岛素敏感性。在三个研究阶段还记录了空腹血清游离脂肪酸（S - FFA）浓度和血浆胃抑制多肽（P - GIP）浓度。与安慰剂相比，普萘洛尔和阿替洛尔均降低了血压、心率和S - FFA浓度，且所有患者的血浆中均检测到了可测量浓度的普萘洛尔和阿替洛尔。因此，这些结果可被视为临床β受体阻滞剂作用的代表。这两种药物对空腹血糖水平无显著影响。与安慰剂相比，普萘洛尔治疗期间空腹和胰高血糖素刺激后的血清C肽浓度有所升高（分别为p = 0.037和p = 0.030），尽管血清胰岛素无显著变化。普萘洛尔和阿替洛尔对胰岛素与红细胞的结合无显著影响，但与安慰剂相比，它们明显降低了葡萄糖消失率KITT（分别为p = 0.0036和p = 0.0003）。这些发现支持了β受体阻滞剂可通过抑制内源性胰岛素分泌以外的机制影响葡萄糖代谢这一观点。
