Instituto de Investigaciones Sanitarias (IDIS), CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain.
Instituto de Investigaciones Sanitarias (IDIS), CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela 15706, Spain; Department of Physiology, CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
Trends Endocrinol Metab. 2016 May;27(5):304-318. doi: 10.1016/j.tem.2016.03.004. Epub 2016 Apr 6.
Glucagon-like peptide 1 (GLP-1) exerts many actions that improve glycemic control. GLP-1 stimulates glucose-stimulated insulin secretion and protects β cells, while its extrapancreatic effects include cardioprotection, reduction of hepatic glucose production, and regulation of satiety. Although an appealing antidiabetic drug candidate, the rapid degradation of GLP-1 by dipeptidyl peptidase 4 (DPP-4) means that its therapeutic use is unfeasible, and this prompted the development of two main GLP-1 therapies: long-acting GLP-1 analogs and DPP-4 inhibitors. In this review, we focus on the pancreatic effects exerted by current GLP-1 derivatives used to treat diabetes. Based on the results from in vitro and in vivo studies in humans and animal models, we describe the specific actions of GLP-1 analogs on the synthesis, processing, and secretion of insulin, islet morphology, and β cell proliferation and apoptosis.
胰高血糖素样肽 1(GLP-1)具有改善血糖控制的多种作用。GLP-1 刺激葡萄糖刺激的胰岛素分泌并保护β细胞,而其胰外作用包括心脏保护、减少肝葡萄糖产生和调节饱腹感。尽管 GLP-1 是一种有吸引力的抗糖尿病药物候选物,但二肽基肽酶 4(DPP-4)对 GLP-1 的快速降解意味着其治疗用途不可行,这促使了两种主要的 GLP-1 治疗方法的发展:长效 GLP-1 类似物和 DPP-4 抑制剂。在这篇综述中,我们重点介绍了目前用于治疗糖尿病的 GLP-1 衍生物对胰腺的作用。根据人类和动物模型的体外和体内研究结果,我们描述了 GLP-1 类似物对胰岛素的合成、加工和分泌、胰岛形态以及β细胞增殖和凋亡的具体作用。