Brand C L, Jørgensen P N, Svendsen I, Holst J J
Immunochemical Department, University of Copenhagen, Denmark.
Diabetes. 1996 Aug;45(8):1076-83. doi: 10.2337/diab.45.8.1076.
Effects of glucagon immunoneutralization on plasma glucose, insulin, and glucagon were studied 2-4 h after intravenous injection of a high-affinity, monoclonal glucagon antibody into normal as well as moderately and severely alloxan (ALX)-induced diabetic rabbits (n = 5-7). A monoclonal trinitrophenyl antibody was used in control studies. Endogenous glucagon was completely neutralized as evidenced by undetectable levels of free glucagon and high plasma glucagon-binding capacities. In postabsorbtive normal rabbits, glucagon neutralization decreased plasma glucose by 2.2 +/- 0.3 mmol/l, and the resulting plasma levels of insulin and glucagon (indirectly measured) were 8 +/- 3 and 640 +/- 129% of baseline, respectively. However, when euglycemia was maintained by means of glucose infusion (steady-state plasma glucose and glucose infusion rate: 6.6 +/- 0.1 mmol/l and 3.0 +/- 0.4 mg.kg-1.min-1), both plasma insulin and glucagon remained unaltered. Thus, the glucose infusion rate accurately reflects glucagon's contribution to postabsorbtive glucose production. In both moderately and severely diabetic rabbits, immunoneutralization of glucagon decreased plasma glucose by approximately 8 mmol/l, leading to euglycemia (7.3 +/- 1.1 mmol/l) and reduced hyperinsulinemia (41 +/- 9% of baseline) in the former and to partial restoration of euglycemia (12.7 +/- 1.8 mmol/l) and unchanged insulin levels in the latter group of diabetic rabbits (P < 0.05 vs. controls in all studies). No significant changes were observed in control studies. In conclusion, glucagon is an important regulator of postabsorbtive glucose production in normal rabbits and plays an important role in the maintenance of hyperglycemia in ALX-induced diabetic rabbits.
在正常以及中度和重度四氧嘧啶（ALX）诱导的糖尿病兔（n = 5 - 7）静脉注射高亲和力单克隆胰高血糖素抗体2 - 4小时后，研究了胰高血糖素免疫中和对血浆葡萄糖、胰岛素和胰高血糖素的影响。在对照研究中使用了单克隆三硝基苯基抗体。内源性胰高血糖素被完全中和，游离胰高血糖素水平检测不到以及血浆胰高血糖素结合能力高证明了这一点。在吸收后正常兔中，胰高血糖素中和使血浆葡萄糖降低2.2±0.3 mmol/l，并且由此产生的血浆胰岛素和胰高血糖素水平（间接测量）分别为基线的8±3%和640±129%。然而，当通过葡萄糖输注维持血糖正常时（稳态血浆葡萄糖和葡萄糖输注速率：6.6±0.1 mmol/l和3.0±0.4 mg·kg-1·min-1），血浆胰岛素和胰高血糖素均保持不变。因此，葡萄糖输注速率准确反映了胰高血糖素对吸收后葡萄糖生成的贡献。在中度和重度糖尿病兔中，胰高血糖素的免疫中和使血浆葡萄糖降低约8 mmol/l，导致前者血糖正常（7.3±1.1 mmol/l）和高胰岛素血症减轻（为基线的41±9%），而后者组糖尿病兔血糖部分恢复正常（12.7±1.8 mmol/l）且胰岛素水平不变（在所有研究中与对照组相比P < 0.05）。在对照研究中未观察到显著变化。总之，胰高血糖素是正常兔吸收后葡萄糖生成的重要调节因子，并且在ALX诱导的糖尿病兔高血糖的维持中起重要作用。
