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胰岛素和胰高血糖素样肽1受体激动剂利拉鲁肽对db/db小鼠肾脏蛋白质组的影响。

Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice.

作者信息

Liljedahl Leena, Norlin Jenny, McGuire James N, James Peter

机构信息

Department of Immunotechnology, Lund University, Lund, Sweden

Novo Nordisk A/S, Måløv, Denmark.

出版信息

Physiol Rep. 2017 Mar;5(6). doi: 10.14814/phy2.13187.

Abstract

Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 -carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1 (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC). Furthermore, the separation of the insulin, liraglutide and vehicle db/db mouse groups in multivariate analyses was not mainly related to the albumin excretion rate (AER) or the level of glycated hemoglobin A (HbA%) in the mice. In summary, we show that insulin and liraglutide give rise to separate protein profiles in the db/db mouse kidney.

摘要

糖尿病(DM)是一种全球性疾病,影响着全球9%的成年人口,其中2型糖尿病占90%。糖尿病的一个常见后果是肾脏并发症,可能导致肾衰竭。我们通过使用db/db小鼠模型系统和质谱(MS)研究了胰岛素和胰高血糖素样肽1受体(GLP-1R)激动剂利拉鲁肽治疗对糖尿病肾脏蛋白质组的潜在影响。多变量分析揭示了胰岛素和利拉鲁肽对db/db肾脏蛋白质组的不同影响,这在例如蝶呤-4-甲醇胺脱水酶/肝细胞核因子-1二聚化辅因子(PCBD1)、神经前体细胞表达发育下调-8(NEDD8)、转录延伸因子-B多肽-1(ELOC)和铁调素(HEPC)的蛋白质水平上可见。此外,在多变量分析中,胰岛素、利拉鲁肽和赋形剂db/db小鼠组的分离主要与小鼠的白蛋白排泄率(AER)或糖化血红蛋白A(HbA%)水平无关。总之,我们表明胰岛素和利拉鲁肽在db/db小鼠肾脏中产生了不同的蛋白质谱。

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