Exendin-4 inhibits interleukin-1β-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F β-cells

• DOI: 10.1677/joe-08-0507
• Publication Date: 2009-04-28T00:59:15Z
• Authors: Jung-Hoon Kang; Seo-Yoon Chang; Hyun-Jong Jang; Dong-Bin Kim; Gyeong Ryul Ryu; Seung Hyun Ko; In-Kyung Jeong; Yang-Hyeok Jo; Myung-Jun Kim
• Keywords: Ex vivo

Cytokines such as interleukin-1β (IL-1β) stimulate inducible nitric oxide synthase (iNOS) expression and overproduction leading to β-cell damage. Meanwhile, glucagon-like peptide-1 (GLP-1) its potent analog exendin-4 (EX-4) were well known for proliferation. However, the protective mechanisms of GLP-1 in β-cells exposed cytokines not fully elucidated. Therefore, effects EX-4 on IL-1β-induced iNOS gene investigated employing RINm5F β-cells. inhibited protein nitrite production. northern blot promoter analyses showed that failed inhibit mRNA activity. By electrophoretic mobility shift assay (EMSA), did alter binding activity NF-κB promoter. Consistent with EMSA result, nuclear translocation p65. We also tested effect stability. Actinomycin D chase experiments affect decay rate using construct containing 3′-untranslated region stability mRNA. forskolin significantly protein, which was reversed by H-89, a kinase A (PKA) inhibitor. Moreover, pretreatment restored decrease cAMP toward control level. Additionally, cycloheximide study demonstrated accelerated degradation. therefore concluded production via cAMP/PKA system irrespective both transcriptional posttranscriptional gene, this inhibitory appears be regulated at posttranslational