Rohner-Jeanrenaud F, Jeanrenaud B
Faculty and Department of Medicine, University of Geneva, Switzerland.
Diabetologia. 1988 Apr;31(4):235-40. doi: 10.1007/BF00290591.
The results reported in the literature regarding glucagonaemia in genetically obese fa/fa rats are conflicting: normal, increased or decreased plasma glucagon levels have been reported. Due to the existence of several molecules endowed with glucagon-like immunoreactivity, it was thought that the conflicting data could be related to the degree of specificity of the different glucagon antibodies. Three antibodies that all qualified as being specific for pancreatic glucagon were used. It was found that, depending on the antibody, absolute values of basal glucagonaemia or arginine-induced glucagon output varied quantitatively and qualitatively in both lean and obese rats. When non-extracted basal or stimulated plasma samples were passed on a G-50 Sephadex column, glucagon-like immunoreactivity was present over a wide range of molecular weights, indicating the presence of non-pancreatic glucagon molecules. When an ethanol extraction was used, the fractions eluting from the G-50 Sephadex column contained only pancreatic glucagon immunoreactivity. It is concluded that ethanol extraction is necessary for the measurement of the 3500 daltons glucagon. Using this methodology it was found that: (1) basal glucagonaemia was low but identical in the two groups of rats; (2) arginine-induced glucagon secretion was greater in obese than in lean animals; (3) glucagonaemia was decreased by glucose administration in lean but not in obese rats. It is concluded that there are, in obese animals, dysfunctions of glucagon output that may play a role in their abnormal glucose tolerance.
文献中报道的关于遗传性肥胖fa/fa大鼠胰高血糖素血症的结果相互矛盾：血浆胰高血糖素水平有正常、升高或降低的报道。由于存在几种具有胰高血糖素样免疫反应性的分子，人们认为相互矛盾的数据可能与不同胰高血糖素抗体的特异性程度有关。使用了三种均被认为对胰腺胰高血糖素具有特异性的抗体。结果发现，取决于所使用的抗体，无论是瘦鼠还是肥胖大鼠，基础胰高血糖素血症的绝对值或精氨酸诱导的胰高血糖素分泌在数量和质量上都有所不同。当未提取的基础或刺激血浆样本通过G-50葡聚糖凝胶柱时，胰高血糖素样免疫反应性在很宽的分子量范围内都存在，这表明存在非胰腺来源的胰高血糖素分子。当使用乙醇提取时，从G-50葡聚糖凝胶柱洗脱的级分仅含有胰腺胰高血糖素免疫反应性。得出的结论是，测量3500道尔顿的胰高血糖素需要进行乙醇提取。使用这种方法发现：（1）两组大鼠的基础胰高血糖素血症较低但相同；（2）肥胖动物中精氨酸诱导的胰高血糖素分泌比瘦动物更多；（3）葡萄糖给药后，瘦鼠的胰高血糖素血症降低，而肥胖大鼠则没有。得出的结论是，在肥胖动物中，胰高血糖素分泌存在功能障碍，这可能在其异常的糖耐量中起作用。
