共查询到20条相似文献,搜索用时 15 毫秒
1.
The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription 总被引:13,自引:0,他引:13
Zhao L Guo M Matsuoka TA Hagman DK Parazzoli SD Poitout V Stein R 《The Journal of biological chemistry》2005,280(12):11887-11894
2.
Background
Type 2 diabetes is characterized by pancreatic β-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that the signalling cascade activated by lipopolysaccharides (LPS) binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets.Methodology/Principal Findings
A 24-h exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of pancreas-duodenum homebox-1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Accordingly, LPS exposure also decreased glucose-induced insulin secretion. LPS repression of insulin, PDX-1 and MafA expression, as well as its inhibition of insulin secretion, were not observed in islets from TLR4-deficient mice. LPS inhibition of β-cell gene expression in rat islets was prevented by inhibition of the NF-κB pathway, but not the p38 mitogen-activated protein kinase (p38 MAPK) pathway.Conclusions/Significance
Our findings demonstrate that LPS inhibit β-cell gene expression in a TLR4-dependent manner and via NF-κB signaling in pancreatic islets, suggesting a novel mechanism by which the gut microbiota might affect pancreatic β-cell function. 相似文献3.
4.
5.
6.
Kaneto H Matsuoka TA Nakatani Y Miyatsuka T Matsuhisa M Hori M Yamasaki Y 《The Journal of biological chemistry》2005,280(15):15047-15052
7.
8.
9.
10.
Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression 总被引:19,自引:0,他引:19
Kaneto H Xu G Fujii N Kim S Bonner-Weir S Weir GC 《The Journal of biological chemistry》2002,277(33):30010-30018
11.
12.
13.
Amemiya-Kudo M Oka J Ide T Matsuzaka T Sone H Yoshikawa T Yahagi N Ishibashi S Osuga J Yamada N Murase T Shimano H 《The Journal of biological chemistry》2005,280(41):34577-34589
14.
15.
16.
17.
Khoo S Griffen SC Xia Y Baer RJ German MS Cobb MH 《The Journal of biological chemistry》2003,278(35):32969-32977
18.
MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene 总被引:12,自引:0,他引:12
Kataoka K Han SI Shioda S Hirai M Nishizawa M Handa H 《The Journal of biological chemistry》2002,277(51):49903-49910
19.