Schmid R, Schusdziarra V, Aulehner R, Weigert N, Classen M
Department of Internal Medicine II, Technical University of Munich, Germany.
Z Gastroenterol. 1990 Jun;28(6):280-4.
The effect of equimolar doses of GIP and GLP-1 (7-36amide) on insulin and somatostatin secretion in the isolated perfused rat pancreas was compared. At a perfusate glucose concentration of 70 mg/dl GLP-1 (7-36amide) 10(-9) and 10(-8) M and GIP 10(-9) M elicited a significant stimulation of insulin while GIP 10(-8) M and lower doses of both peptides (10(-11) and 10(-10) M) were ineffective. At elevated perfusate glucose levels of 150 mg/dl both peptides stimulated insulin release at 10(-11), 10(-10), 10(-9) and 10(-8) M but not at 10(-12) M. The insulin response at the higher glucose level was significantly greater compared to the effect of the same doses at normoglycemic conditions. Somatostatin release was stimulated significantly by GLP-1 (7-36amide) at 10(-10) and 10(-9) M at perfusate glucose level 70 mg/dl. At a glucose concentration of 150 mg/dl this effect was abolished. GIP did not alter somatostatin release at a perfusate glucose concentration of 70 mg/dl while at 150 mg/dl only the highest dose of GIP (10(-8) M) stimulated somatostatin release significantly. In conclusion, the present data demonstrate that in vitro in the rat pancreas both peptides are equally effective secretagogues of insulin release at normal and moderately elevated perfusate glucose levels. In contrast, somatostatin secretion is stimulated by GLP-1 (7-36amide) at normoglycemic conditions while only a rather high and presumably pharmacological dose of GIP is a stimulus of somatostatin secretion at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
比较了等摩尔剂量的葡萄糖依赖性促胰岛素多肽(GIP)和胰高血糖素样肽-1(7-36酰胺)对离体灌注大鼠胰腺胰岛素和生长抑素分泌的影响。在灌注液葡萄糖浓度为70mg/dl时,10^(-9)M和10^(-8)M的胰高血糖素样肽-1(7-36酰胺)以及10^(-9)M的GIP能显著刺激胰岛素分泌,而10^(-8)M的GIP以及两种多肽的较低剂量(10^(-11)M和10^(-10)M)则无效。在灌注液葡萄糖水平升高至150mg/dl时,两种多肽在10^(-11)M、10^(-10)M、10^(-9)M和10^(-8)M时均能刺激胰岛素释放,但在10^(-12)M时则不能。与正常血糖条件下相同剂量的作用相比,较高葡萄糖水平时的胰岛素反应明显更大。在灌注液葡萄糖水平为70mg/dl时,10^(-10)M和10^(-9)M的胰高血糖素样肽-1(7-36酰胺)能显著刺激生长抑素释放。在葡萄糖浓度为150mg/dl时,这种作用消失。在灌注液葡萄糖浓度为70mg/dl时,GIP不改变生长抑素释放,而在150mg/dl时,只有最高剂量的GIP(10^(-8)M)能显著刺激生长抑素释放。总之,目前的数据表明,在大鼠胰腺体外实验中,在正常和适度升高的灌注液葡萄糖水平下,两种多肽都是胰岛素释放的同等有效的促分泌剂。相比之下,在正常血糖条件下,胰高血糖素样肽-1(7-36酰胺)刺激生长抑素分泌,而在中度高血糖时,只有相当高且可能是药理剂量的GIP才是生长抑素分泌的刺激因素。(摘要截短至2