Epidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice

Epidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice
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DOI:
10.1111/j.1582-4934.2007.00169.x
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发表时间:
2008-09-01
影响因子:
5.3
通讯作者:
Ryu, S. H.
Ryu, S. H.
中科院分区:
医学2区
文献类型:
--
作者:
Lee, H. Y.;Yea, K.;Ryu, S. H.

文献摘要

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表皮生长因子(EGF)在胰腺中合成,糖尿病动物的EGF水平较低。然而,EGF在调节胰腺的主要功能,胰岛素分泌中的作用尚未研究。在这里,我们表明,EGF迅速增加小鼠胰岛中的胰岛素分泌,以及在胰腺β细胞系。这些事件依赖于Ca2+内流和磷脂酶D(PLD)活性,特别是PLD 2,如使用药理学阻断剂和分子操作,如PLD同工酶的过表达和siRNA确定。此外,EGF还增加血浆胰岛素水平,并介导正常和糖尿病小鼠的血糖降低。在这里,我们第一次提供证据表明EGF是一种新型促分泌素,可调节血糖水平,并可用于开发糖尿病治疗药物。
Epidermal growth factor (EGF) is synthesized in the pancreas and diabetic animals have low levels of EGF. However, the role of EGF in regulating the major function of the pancreas, insulin secretion, has not been studied. Here, we show that EGF rapidly increased insulin secretion in mouse pancreatic islets, as well as in a pancreatic beta-cell line. These events were dependent on a Ca2+ influx and phospholipase D (PLD) activity, particularly PLD2, as determined using pharmacological blockers and molecular manipulations such as over-expression and siRNA of PLD isozymes. In addition, EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice. Here, for the first time, we provide evidence that EGF is a novel secretagogue that regulates plasma glucose levels and a candidate for the development of therapeutics for diabetes.