Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance.
Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance.
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DOI：
10.1007/s00125-014-3490-7
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发表时间：
2015-04
期刊：
影响因子：
8.2
通讯作者：
Blueher, Matthias
中科院分区：
文献类型：
--
作者：
Kannt, Aimo;Pfenninger, Anja;Teichert, Lenore;Toenjes, Anke;Dietrich, Arne;Schon, Michael R.;Kloeting, Nora;Blueher, Matthias
关键词：
烟酰胺-N-甲基转移酶（NNMT）最近被证明在胰岛素抵抗和肥胖的小鼠模型中上调。到目前为止，还不清楚NNMT是否在人类疾病中受到调节。我们探讨了白色脂肪组织（WAT）NNMT表达和血浆1-甲基烟酰胺（MNA）浓度在人胰岛素抵抗和2型糖尿病中增加的假设。 在三组个体中分析NNMT表达和血浆MNA：（1）199例接受腹部手术的患者;（2）60例接受12周运动计划的患者和（3）55例接受两步减肥手术计划的患者。与对照组相比，显性2型糖尿病患者在网膜和皮下WAT中的NNMT表达显著（约两倍）升高。值得注意的是，在2型糖尿病患者中血浆MNA与WAT NNMT表达显著相关（女性，r = 0.59，p < 0.001;男性，r = 0.61，p < 0.001），但在健康对照个体中不相关。在胰岛素抵抗个体中，胰岛素敏感性与血浆MNA（r = 0.44，p = 0.01）或脂肪组织NNMT mRNA（r = 0.64，p < 0.001）呈负相关。后一种关联在第二个队列中得到证实（n = 60，r = 0.78，p < 0.001）。改善胰岛素敏感性的干预措施-运动和减肥手术-与WAT NNMT表达的显著降低相关（p < 0.001）。减肥手术也与血浆MNA显著降低相关。我们证明，WAT NNMT表达在人类胰岛素抵抗和2型糖尿病中受到调节，血浆MNA与组织NNMT表达增加和胰岛素抵抗程度相关，使其成为胰岛素敏感性丧失的潜在生物标志物。本文的在线版本（doi：10.1007/s 00125 -014-3490-7）包含同行评审但未经编辑的补充材料，可供授权用户使用。
Nicotinamide-N-methyltransferase (NNMT) was recently shown to be upregulated in mouse models of insulin resistance and obesity. So far, it is unknown whether NNMT is regulated in human disease. We have explored the hypothesis that white adipose tissue (WAT) NNMT expression and plasma 1-methylnicotinamide (MNA) concentration are increased in human insulin resistance and type 2 diabetes. NNMT expression and plasma MNA were analysed in three groups of individuals: (1) 199 patients undergoing abdominal surgery; (2) 60 individuals on a 12-week exercise programme and (3) 55 patients on a two-step bariatric surgery programme. Patients with manifest type 2 diabetes have a significantly (approximately twofold) higher NNMT expression both in omental and subcutaneous WAT compared with controls. Notably, plasma MNA correlated significantly with WAT NNMT expression in patients with type 2 diabetes (women, r = 0.59, p < 0.001; men, r = 0.61, p < 0.001) but not in healthy control individuals. In insulin-resistant individuals, there was an inverse correlation between insulin sensitivity and plasma MNA (r = 0.44, p = 0.01) or adipose tissue NNMT mRNA (r = 0.64, p < 0.001). The latter association was confirmed in a second cohort (n = 60, r = 0.78, p < 0.001). Interventions improving insulin sensitivity—exercise and bariatric surgery—were associated with a significant (p < 0.001) reduction in WAT NNMT expression. Bariatric surgery was also associated with a significant decrease in plasma MNA. We demonstrate that WAT NNMT expression is regulated in human insulin resistance and type 2 diabetes and that plasma MNA correlates with increased tissue NNMT expression and the degree of insulin resistance, making it a potential biomarker for loss of insulin sensitivity. The online version of this article (doi:10.1007/s00125-014-3490-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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影响因子：
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作者：
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