然而理论上,以GLP-1为基础的嵌合工程可以扩展到结构完全不同的激素,因为多价化学融合或耦连是可行的,其中第二效应分子可以从小的寡核苷酸、核激素到多肽和大的蛋白质。 GLP-1与胃泌素、胰淀素、胆囊收缩素(CCK)之间的分子融合已有报道,还有与更大的蛋白如F...
miniGq、miniGi）耦合作用显著降低；在高浓度的GLP-1（100 nM）作用下，虽然GLPLight1表现出强荧光响应...
天然GLP-1是有31个氨基酸残基的多肽,在食物的刺激下由小肠L细胞分泌,在血液中有GLP-1(7-36)、GLP-1(7-37)两种活性结构,对二型糖尿病及肥胖症均有较好的调控作用,但其在人体内半衰期仅有2-3min,不具备药用价值。诺和诺德在GLP-1的基础上成功开发出了每日一次的利...
尽管GLP-1有诸多优点,但临床开发最致命弱点是GLP-1在血液中的半衰期较短,主要原因有两个:一是因为被受体内二肽基肽酶4 (DPP-4) 以及中性肽链内切酶(NEP)所降解,两者的切割会使GLP-1失活。二是GLP-1在体内会被肾脏清除而快速降解,这使得内生GLP-1在体内的半衰期约为 2 min,且只有 10-15% 的GLP-1 完整...
[4] Hui, H., Farilla, L., Merkel, P., Perfetti, R. 2002. The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol 146:863-869. [5] Deacon, C.F., Johnsen, A.H., Holst, J.J. 1995. Degradation of glucago...
GLP-1fatty acidamino acidenteroendocrine cellsappetiteobesityObesity is a risk factor for cardiometabolic diseases. Nutrients stimulate GLP-1 release; however, GLP-1 has a short half-life (<2 min), and only <10–15% reaches the systemic circulation. Human L-cells are localized i...
Because of the short biological half-life of GLP-1, the endocrine action may be relevant only after substan- tial stimulation of GLP-1 release or pharmacological interventions. Although hindbrain circuitries alone can mediate the satiating effect of hindbrain GLP-1 receptor (GLP-1R) stimulation, ...
glp1作用机制.pptx,内容提要2型糖尿病治疗的现状与挑战肠促胰素概述GLP-1及其作用机制胰岛α细胞产生过多胰高糖素β细胞产生胰岛素减少胰岛素减少胰岛素减少胰岛素抵抗 (葡萄糖摄取减少)糖输出过多2型糖尿病的病理生理包括三方面主要缺陷 胰岛素不足胰腺过多胰高糖素高血糖
The plasma half-life of GLP-1(28-36)amide is longer in human hepatocytes (t1/2 = 24 min) than that in mouse hepatocytes (t1/2 = 13 min)[1]. The administration of GLP-1(28-36)amide at a rate of 18.5 nmol/kg BW/day for 9 weeks to diet-induced obese mice diminishes the ...
It retains 97% sequence homology to human GLP-1. Acylation prolongs the half-life of GLP-1 by slowing release from the injection site; and extensive binding to albumin, which protects it from degradation by DPP-4 and reduced renal clearance). Glucagon-Like Peptide-1 Receptors Agonists (GLP1...