Effects of vaspin on pancreatic β cell secretion via PI3K/Akt and NF-κB signaling pathways.
Effects of vaspin on pancreatic β cell secretion via PI3K/Akt and NF-κB signaling pathways.
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Vaspin 通过 PI3K/Akt 和 NF-kappa B 信号通路对胰腺 β 细胞分泌的影响
DOI：
10.1371/journal.pone.0189722
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li N
中科院分区：
文献类型：
--
作者：
Liu S;Li X;Wu Y;Duan R;Zhang J;Du F;Zhang Q;Li Y;Li N
Vaspin（内脏脂肪组织衍生丝氨酸蛋白酶抑制剂）是最近发现的一种脂肪因子，与糖尿病和其他代谢紊乱有关。然而，vaspin对胰腺β细胞功能的影响及其相关机制尚不完全清楚。因此，本研究旨在探讨vaspin对胰腺β细胞功能的影响及其潜在机制。在体外（大鼠胰岛素瘤细胞，INS-1）和体内（高脂饲料喂养大鼠）进行实验。结果显示，vaspin显著提高了INS-1细胞的分泌功能。利用抑制剂、western blot和实时PCR技术探索其潜在机制。我们发现vaspin增加了IRS-2 mRNA和IRS-2总蛋白的水平，而降低了IRS-2蛋白的丝氨酸磷酸化水平。此外，vaspin增加了Akt磷酸化蛋白水平，这被PI3K抑制剂ly294002逆转。此外，vaspin增加了mTOR和p70S6K的磷酸化水平，而这种磷酸化水平被雷帕霉素抑制。同时，我们发现vaspin处理后，NF-κB mRNA和蛋白水平降低，与NF-κB抑制剂TPCK的作用相似。此外，vaspin增加高脂饲料大鼠葡萄糖刺激胰岛素分泌（GSIS）水平，降低血糖水平，改善糖耐量和胰岛素敏感性。高血糖钳夹试验显示血管素改善胰岛β细胞功能。总之，这些发现为vaspin对胰腺β细胞的功能提供了新的认识，并提示它可能作为预防和治疗2型糖尿病的潜在药物。
Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a recently discovered adipokine that has been implicated in diabetes mellitus and other metabolic disorders. However, the effects of vaspin on pancreatic β cell function and related mechanisms are not fully understood. Thus, the present study was performed to investigate the effects of vaspin on pancreatic β cell function and the potential underlying mechanisms. Both in vitro (rat insulinoma cells, INS-1) and in vivo (high fat diet fed rats) experiments were conducted. The results showed that vaspin significantly increased INS-1 cell secretory function. Potential mechanisms were explored using inhibitors, western blot and real-time PCR techniques. We found that vaspin increased the levels of IRS-2 mRNA and IRS-2 total protein, while decreased the serine phosphorylation level of IRS-2 protein. Moreover, vaspin increased the Akt phosphorylation protein level which was reversed by PI3K inhibitor ly294002. In addition, vaspin increased the phosphorylation levels of mTOR and p70S6K, which was inhibited by rapamycin. Meanwhile, we found that the NF-κB mRNA and protein levels were reduced after vaspin treatment, similar to the effect of NF-κB inhibitor TPCK. Furthermore, vaspin increased the glucose stimulated insulin secretion (GSIS) level, lowered blood glucose level and improved the glucose tolerance and insulin sensitivity of high fat diet fed rats. Hyperglycemic clamp test manifested that vaspin improved islet β cell function. Together, these findings provide a new understanding of the function of vaspin on pancreatic β cell and suggest that it may serve as a potential agent for the prevention and treatment of type 2 diabetes.
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影响因子：
3.7
作者：
Cui W;Ma J;Wang X;Yang W;Zhang J;Ji Q
通讯作者：
Ji Q
DOI：
10.1083/jcb.200403069
发表时间：
2004-07-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harrington LS;Findlay GM;Gray A;Tolkacheva T;Wigfield S;Rebholz H;Barnett J;Leslie NR;Cheng S;Shepherd PR;Gout I;Downes CP;Lamb RF
通讯作者：
Lamb RF
影响因子：
5.3
作者：
Assmann, Anke;Ueki, Kohjiro;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.
影响因子：
5.1
作者：
KAWANO, K;HIRASHIMA, T;NATORI, T
通讯作者：
NATORI, T
影响因子：
7.7
作者：
Donath, MY;Ehses, JA;Reinecke, M
通讯作者：
Reinecke, M