当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE期刊下所有文献 > Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets.

Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets.

Abstract：

:The number of pro-α cells is known to increase in response to β cell injury and these cells then generate glucagon-like peptide-1 (GLP-1), thus attenuating the development of diabetes. The aim of the present study was to further examine the role and the mechanisms responsible for intra-islet GLP-1 production as a self-protective response against lipotoxicity. The levels of the key enzyme, prohormone convertase 1/3 (PC1/3), as well as the synthesis and release of GLP-1 in models of lipotoxicity were measured. Furthermore, islet viability, apoptosis, oxidative stress and inflammation, as well as islet structure were assessed after altering GLP-1 receptor signaling. Both prolonged exposure to palmitate and a high-fat diet facilitated PC1/3 expression, as well as the synthesis and release of GLP-1 induced by β cell injury and the generation of pro-α cells. Prolonged exposure to palmitate increased reactive oxygen species (ROS) production, and the antioxidant, N-acetylcysteine (NAC), partially prevented the detrimental effects induced by palmitate on β cells, resulting in decreased GLP-1 levels. Furthermore, the inhibition of GLP-1 receptor (GLP-1R) signaling by treatment with exendin‑(9-39) further decreased cell viability, increased cell apoptosis and caused a stronger inhibition of the β cell-specific transcription factor, pancreatic duodenal homeobox 1 (PDX1). Moreover, treatment with the GLP-1R agonist, liraglutide, normalized islet structure and function, resulting in a decrease in cell death and in the amelioration of β cell marker expression. Importantly, liraglutide maintained the oxidative balance and decreased inflammatory factor and p65 expression. Overall, our data demonstrate that an increase in the number of pro-α cells and the activation of the intra-islet GLP-1 system comprise a self-defense mechanism for enhancing β cell survival to combat lipid overload, which is in part mediated by oxidative stress and inflammation.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Huang C,Yuan L,Cao S

doi

10.3892/ijmm.2015.2207

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

173-85

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

在线工具

Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets.