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肠-胰岛轴:新型肠促胰岛素候选药物胰高血糖素样肽-1(7-36)酰胺(GLP-1(7-36)酰胺)

[The entero-insular axis: the new incretin candidate glucagon-like peptide-1(7-36)amide (GLP-1(7-36))amide].

作者信息

Göke R, Göke B, Richter G, Arnold R

机构信息

Zentrum Innere Medizin, Abteilung Gastroenterologie, Stoffwechsel der Philipps-Universität, Marburg.

出版信息

Z Gastroenterol. 1988 Nov;26(11):715-9.

PMID:2849249
Abstract

The functional connection between the gut and pancreatic islets is described by the term "enteroinsular axis". A humoral factor of the gut that might enhance the glucose-induced secretion of insulin is named "incretin". For many years glucose-dependent insulin-releasing polypeptide (GIP) was the strongest incretin candidate. However, recent evidence suggests that glucagon-like peptide-1(7-36)amide represents a more potent physiological incretin. The sequence of GLP-1 is identical in various mammals including man. The 7-36 sequence of the original peptide is a potent insulin-releasing peptide in vitro and in vivo. GLP-1(7-36)amide was found in the human bowel; its circulating level rises in answer to oral glucose and after meals. Recently, specific high-affinity binding sites for GLP-1(7-36)amide were demonstrated on rat insulinoma-derived RINm5F cells. In this model system for B-cell studies the peptide has potent stimulatory effects on cAMP formation, insulin-mRNA transcript synthesis, and insulin release. Further studies in the insulinotropic action of GLP-1(7-36) amide in health and disease will be of great importance.

摘要

肠道与胰岛之间的功能联系用术语“肠胰岛轴”来描述。一种可能增强葡萄糖诱导的胰岛素分泌的肠道体液因子被称为“肠促胰岛素”。多年来,葡萄糖依赖性促胰岛素多肽(GIP)一直是最强的肠促胰岛素候选物。然而,最近的证据表明,胰高血糖素样肽-1(7-36)酰胺是一种更有效的生理性肠促胰岛素。在包括人类在内的各种哺乳动物中,GLP-1的序列是相同的。原始肽的7-36序列在体外和体内都是一种有效的胰岛素释放肽。在人类肠道中发现了GLP-1(7-36)酰胺;其循环水平在口服葡萄糖后和餐后会升高。最近,在大鼠胰岛素瘤来源的RINm5F细胞上证实了GLP-1(7-36)酰胺的特异性高亲和力结合位点。在这个用于B细胞研究的模型系统中,该肽对cAMP形成、胰岛素mRNA转录合成和胰岛素释放具有强大的刺激作用。进一步研究GLP-1(7-36)酰胺在健康和疾病中的促胰岛素作用将非常重要。

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