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胰高血糖素和胰高血糖素样肽-1 作为新型抗炎和免疫调节化合物。

Glucagon and glucagon-like peptide-1 as novel anti-inflammatory and immunomodulatory compounds.

机构信息

Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, n°4365, Manguinhos, CEP 21040-360 Rio de Janeiro, Brazil.

Laboratório de Inflamação, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, n°4365, Manguinhos, CEP 21040-360 Rio de Janeiro, Brazil; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Brazil.

出版信息

Eur J Pharmacol. 2017 Oct 5;812:64-72. doi: 10.1016/j.ejphar.2017.07.015. Epub 2017 Jul 6.

Abstract

Glucagon and glucagon-like peptide-1 (GLP-1) are polypeptide hormones that are produced by pancreatic α-cells and the intestine, respectively, whose main function is to control glucose homeostasis. The glucagon and GLP-1 levels are imbalanced in diabetes. Furthermore, type 1 diabetic patients and animals present with a diminished inflammatory response, which is related to some morbidities of diabetes, such as a higher incidence of infectious diseases, including sepsis. The focus of this review is to briefly summarize the state of the art concerning the effects of glucagon and GLP-1 on the inflammatory response. Here, we propose that glucagon and GLP-1 have anti-inflammatory properties, making them possible prototypes for the design and synthesis of new compounds to treat inflammatory diseases. In addition, glucagon, GLP-1 or their analogues or new derivatives may not only be important for managing inflammatory diseases but may also have the therapeutic potential to prevent, cure or ameliorate diabetes in patients by counteracting the deleterious effects of pro-inflammatory cytokines on the function and viability of pancreatic β-cells. In addition, GLP-1, its analogues or drugs that inhibit GLP-1 metabolism may have a doubly beneficial effect in diabetic patients by inhibiting the inflammatory response and reducing glycaemia.

摘要

胰高血糖素和胰高血糖素样肽-1(GLP-1)是分别由胰腺α细胞和肠道产生的多肽激素,其主要功能是控制葡萄糖稳态。糖尿病患者的胰高血糖素和 GLP-1 水平失衡。此外,1 型糖尿病患者和动物表现出炎症反应减弱,这与糖尿病的一些病态有关,例如传染病的发生率更高,包括败血症。本综述的重点是简要总结胰高血糖素和 GLP-1 对炎症反应的影响。在这里,我们提出胰高血糖素和 GLP-1 具有抗炎特性,使它们成为设计和合成新化合物以治疗炎症性疾病的可能原型。此外,胰高血糖素、GLP-1 或其类似物或新衍生物不仅对治疗炎症性疾病很重要,而且还可能通过对抗促炎细胞因子对胰岛β细胞功能和活力的有害影响,具有预防、治疗或改善糖尿病患者的治疗潜力。此外,GLP-1 及其类似物或抑制 GLP-1 代谢的药物通过抑制炎症反应和降低血糖可能对糖尿病患者产生双重有益作用。

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