Glucose enhances rat islet function via stimulating CART expression
Glucose enhances rat islet function via stimulating CART expression
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葡萄糖通过刺激 CART 表达增强大鼠胰岛功能
DOI：
10.1016/j.bbrc.2016.11.012
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发表时间：
2016
影响因子：
3.1
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Xu Wan;Zhang Yuqing;Bai Mengyao;Zhou Feiye;Deng Ruyuan;Ji Xueying;Zhang Juan;Liu Yun;Zhou Libin;Wang Xiao;Zhou LB;Wang X
可卡因和苯丙胺调节转录物（CART）是一种广泛表达于中枢和外周神经系统以及内分泌细胞中的促肾上腺皮质激素生成肽。CART在几种2型糖尿病啮齿动物模型的β细胞中显著上调。外源性CART肽对胰岛素分泌的刺激作用是cAMP依赖性的。葡萄糖是胰岛功能最重要的调节因子。然而，CART在葡萄糖增强的胰岛素分泌中的作用仍不清楚。在这里，我们的研究结果表明，葡萄糖的时间和剂量依赖性引起CART mRNA在大鼠胰岛的表达。葡萄糖激酶激动剂GKA 50和长效GLP-1类似物exendin-4均增加CART mRNA表达。蛋白激酶A（PKA）抑制剂H89和cAMP反应元件结合蛋白（CREB）的失活抑制毛喉素刺激的CART mRNA表达。此外，CART过度表达增加了大鼠胰岛对葡萄糖和毛喉素的胰岛素分泌，并改善了地塞米松受损的胰岛素分泌。这些发现表明胰岛衍生的CART至少部分参与了高糖增强的胰腺β细胞功能。
Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide widely expressed in the central and peripheral nervous systems, as well as in endocrine cells. CART is markedly upregulated in the β-cells of several rodent models of type-2 diabetes. The stimulatory effect of exogenous CART peptide on insulin secretion is cAMP dependent. Glucose is the most important regulator of islet function. However, the role of CART in glucose-potentiated insulin secretion remains unclear. Here, our results showed that glucose time- and dose-dependently elicited CART mRNA expression in rat islets. Both the glucokinase agonist GKA50 and the long-acting GLP-1 analogue exendin-4 increased CART mRNA expression. The protein kinase A (PKA) inhibitor H89 and the inactivation of cAMP response element-binding protein (CREB) suppressed forskolin-stimulated CART mRNA expression. Furthermore, CART overexpression amplified insulin secretion from rat islets in response to glucose and forskolin, and ameliorated dexamethasone-impaired insulin secretion. These findings suggest that islet-derived CART is involved, at least in part, in high glucose-potentiated pancreatic β-cell function.