Lippl Florian, Kircher Florian, Erdmann Johannes, Allescher Hans-Dieter, Schusdziarra Volker
Department of Internal Medicine II, Technical University of Munich, Ismaningerstr. 22, 81675 Munich, Germany.
Regul Pept. 2004 Jun 15;119(1-2):93-8. doi: 10.1016/j.regpep.2004.01.003.
Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7-36)amide 10(-8) and 10(-7) M decreased ghrelin secretion significantly. In contrast, GIP 10(-8) and 10(-7) M augmented not only prestimulated, but also basal ghrelin secretion (p<0.05). Insulin reduced ghrelin at 10(-10), 10(-8) and 10(-6) M (p<0.05). Both gastrin 10(-8) M and somatostatin 10(-6) M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7-36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.
人体内胃饥饿素的释放取决于测试餐的常量营养素组成。导致这种差异调节的机制在很大程度上尚不清楚。为了阐明它们的潜在作用，研究了胰高血糖素样肽-1（GLP-1）、胃抑制多肽（GIP）、胰岛素、胃泌素和生长抑素对离体大鼠胃饥饿素分泌的影响，这具有避免全身相互作用的优势。基础胃饥饿素分泌处于一个无法持续评估抑制作用的范围内。因此，在迷走神经预刺激期间分析了胃肠激素和胰岛素的作用。GLP-1（7-36）酰胺10⁻⁸和10⁻⁷ M显著降低胃饥饿素分泌。相比之下，GIP 10⁻⁸和10⁻⁷ M不仅增加了预刺激后的胃饥饿素分泌，还增加了基础胃饥饿素分泌（p<0.05）。胰岛素在10⁻¹⁰、10⁻⁸和10⁻⁶ M时降低胃饥饿素分泌（p<0.05）。胃泌素10⁻⁸ M和生长抑素10⁻⁶ M也显著抑制胃饥饿素分泌。这些数据表明，GLP-1（7-36）酰胺、胰岛素、胃泌素和生长抑素可能是导致餐后观察到的胃饥饿素分泌抑制的潜在因素，在这个离体胃模型中胰岛素是最有效的抑制剂。另一方面，GIP可能会减弱餐后胃饥饿素的下降。由于富含蛋白质的餐食不能有效刺激GIP释放，其他尚未明确的肠道因素必定是蛋白质诱导胃饥饿素释放的原因。
