Altered expression of glucagon-like peptide-1 and dipeptidyl peptidase IV in patients with HCV-related glucose intolerance
Altered expression of glucagon-like peptide-1 and dipeptidyl peptidase IV in patients with HCV-related glucose intolerance
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DOI：
10.1111/j.1440-1746.2007.05183.x
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发表时间：
2008-02-01
影响因子：
4.1
通讯作者：
Sata, Michio
中科院分区：
文献类型：
--
作者：
Itou, Minoru;Kawaguchi, Takumi;Sata, Michio
背景和目的：丙型肝炎病毒（HCV）相关的葡萄糖耐受不良的发病机制尚不清楚。胰高血糖素样肽-1（GLP-1）是一种肠道激素，可合成肝糖原，并被二肽基肽酶IV（DPPIV）灭活。本研究的目的是探讨GLP-1和DPPIV的表达在HCV相关的glucose intolerance.Methods的改变：我们招募了HCV或肝炎B病毒（HBV）相关的肝脏疾病（n = 94和37，分别），炎症性肠病（IBD; n = 14）作为疾病对照，和健康对照（n = 48）的患者。血清或组织GLP-1和DPPIV表达水平通过酶免疫测定、免疫印迹或免疫染色测定。采用过碘酸-希夫染色法测定肝糖原含量。HCV组（4.9 ± 0.3 ng/mL）血清GLP-1水平显著低于对照组（7.5 ± 0.6 ng/mL）、HBV组（7.0 ± 0.5 ng/mL）或IBD组（10.8 ± 1.0 ng/mL，P < 0.01）。虽然对照组和HCV组之间回肠GLP-1表达没有显著差异，但HCV组中回肠、肝脏和血清中DPPIV表达显著增加。HCV组肝糖原含量较HBV组下降更明显（127.5 ± 5.3 vs 187.7 ± 6.6任意单位; n = 19，P < 0.01）。结论：我们证实了HCV相关性糖耐量异常患者GLP-1和DPPIV表达的改变。由于肝糖原合成（GLP-1作用）受损，GLP-1和DPPIV表达的改变可能参与HCV相关葡萄糖耐受不良的发展。
Background and Aim: The pathogenesis of hepatitis C virus (HCV)-associated glucose intolerance remains unclear. Glucagon-like peptide-1 (GLP-1), a gut hormone, synthesizes hepatic glycogen and is inactivated by dipeptidyl peptidase IV (DPPIV). The aims of this study were to investigate the alterations in the expression of GLP-1 and DPPIV in HCV-associated glucose intolerance.Methods: We enrolled patients with HCV- or hepatitis B virus (HBV)-related liver disease (n = 94 and 37, respectively), patients with inflammatory bowel disease (IBD; n = 14) as disease controls, and healthy controls (n = 48). The serum or tissue GLP-1 and DPPIV expression levels were determined by enzyme immunoassay, immunoblotting, or immunostaining. The hepatic glycogen content was assayed by periodic acid-Schiff staining.Results: The serum GLP-1 levels were significantly decreased in the HCV group (4.9 +/- 0.3 ng/mL) than those in the controls (7.5 +/- 0.6 ng/mL), the HBV group (7.0 +/- 0.5 ng/mL), or the IBD group (10.8 +/- 1.0 ng/mL, P < 0.01). Although the ileum GLP-1 expression was not significantly different between the controls and the HCV group, the DPPIV expression was significantly increased in the ileum, liver, and serum in the HCV group. Hepatic glycogen content was decreased to a greater extent in the HCV group than that in the HBV group (127.5 +/- 5.3 vs 187.7 +/- 6.6 arbitrary units; n = 19, P < 0.01).Conclusions: We demonstrated the altered expressions of GLP-1 and DPPIV in patients with HCV-associated glucose intolerance. Since hepatic glycogen synthesis, a GLP-1 action, was impaired, the altered expressions of GLP-1 and DPPIV may be involved in the development of HCV-associated glucose intolerance.