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NAG-1/GDF15对高脂饮食/链脲佐菌素诱导的小鼠的抗糖尿病作用。

The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice.

作者信息

Lertpatipanpong Pattawika, Lee Jaehak, Kim Ilju, Eling Thomas, Oh Seung Yeon, Seong Je Kyung, Baek Seung Joon

机构信息

Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.

National Institute of Environmental Health Science, 111 TW Alexander Dr. Research Triangle Park, NC, 27709, USA.

出版信息

Sci Rep. 2021 Jul 22;11(1):15027. doi: 10.1038/s41598-021-94581-y.

DOI:10.1038/s41598-021-94581-y
PMID:34294853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8298384/
Abstract

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.

摘要

非甾体抗炎药激活基因-1（NAG-1）在多种疾病中发挥作用。在此，我们使用高脂饮食/链脲佐菌素诱导的糖尿病小鼠模型评估了NAG-1的抗糖尿病作用。与野生型（WT）小鼠相比，过表达NAG-1的转基因（NAG-1 Tg）小鼠体重、空腹血糖水平和血清胰岛素水平更低。NAG-1 Tg小鼠胰岛素抵抗评分的稳态模型评估低于WT小鼠。苏木精和伊红染色显示，与WT小鼠相比，NAG-1 Tg小鼠脂肪组织中的脂滴尺寸更小，肝细胞中的脂质积累更少，胰腺中的β细胞面积更大。免疫组织化学分析显示，NAG-1 Tg小鼠β细胞中凋亡标志物半胱天冬酶-3的裂解表达下调。NAG-1 Tg小鼠中脂联素和瘦素mRNA水平分别上调和下调。此外，NAG-1 Tg小鼠中IRS1/PI3K/AKT信号通路成分的表达，尤其是调节肌肉和白色脂肪组织糖异生的Foxo1的表达下调。此外，NAG-1过表达促进了肌肉和脂肪细胞中As160的表达，NAG-1 Tg小鼠中NLRP3通路成员的mRNA水平下调。我们的研究结果表明，NAG-1表达可减轻小鼠糖尿病症状。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2f/8298384/42d24039d053/41598_2021_94581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2f/8298384/b59199fd3ab0/41598_2021_94581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2f/8298384/8784efd91f3c/41598_2021_94581_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2f/8298384/baf06a6bcdcd/41598_2021_94581_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2f/8298384/191f0783f2f1/41598_2021_94581_Fig9_HTML.jpg

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