Insulin enhanced leptin-induced STAT3 signaling by inducing GRP78.

Insulin enhanced leptin-induced STAT3 signaling by inducing GRP78.
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DOI:
10.1038/srep34312
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发表时间:
2016-09-28
期刊:
影响因子:
4.6
通讯作者:
Ozawa K
Ozawa K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Thon M;Hosoi T;Ozawa K

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瘦素是一种脂肪细胞产生的激素,中枢调节能量稳态。据报道,瘦素和胰岛素在葡萄糖和能量稳态调节中存在重叠。然而,胰岛素对瘦素在中枢神经系统(CNS)中的作用尚未详细阐明。在本研究中,我们发现胰岛素通过GRP 78在神经元细胞系SH-SY 5 Y-ObRb中增强瘦素的作用。由于胰岛素诱导GRP 78,我们推测它也可能通过这种诱导增强瘦素的作用。我们发现,胰岛素增强瘦素诱导的STAT 3磷酸化,这种作用被GRP 78的敲低所改善。GRP 78在瘦素作用中的作用也通过瘦素诱导的STAT 3磷酸化在其中GRP 78被敲低的HEK 293-ObRb细胞中的损伤来证实。此外,我们发现GRP 78的过表达增强瘦素诱导的STAT 3磷酸化。这些结果表明GRP 78在瘦素的作用中起重要作用。此外,胰岛素可以通过诱导GRP 78来增强瘦素诱导的STAT 3的活化,这可能在CNS中提供胰岛素和瘦素之间的重要联系。
Leptin, an adipocyte-derived hormone, centrally regulates energy homeostasis. Overlaps in the regulation of glucose and energy homeostasis have been reported between leptin and insulin. However, the effects of insulin on leptin’s actions in the central nervous system (CNS) have not yet been elucidated in detail. In the present study, we found that insulin potentiated leptin’s actions through GRP78 in the neuronal cell line, SH-SY5Y-ObRb. Since insulin induces GRP78, we speculated that it may also enhance leptin’s actions through this induction. We found that insulin enhanced leptin-induced STAT3 phosphorylation and this effect was ameliorated by the knockdown of GRP78. The role of GRP78 in leptin’s actions was also confirmed by impairments in leptin-induced STAT3 phosphorylation in HEK293-ObRb cells in which GRP78 was knocked down. Furthermore, we found that the overexpression of GRP78 enhanced leptin-induced STAT3 phosphorylation. These results suggest that GRP78 plays an important role in leptin’s actions. Furthermore, insulin may enhance the leptin-induced activation of STAT3 by inducing GRP78, which may provide an important connection between insulin and leptin in the CNS.
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