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胰岛素和胰岛素样生长因子1(IGF-1)调节星形胶质细胞胞质内的葡萄糖和糖原水平,但不调节跨膜葡萄糖转运。

Insulin and Insulin-like Growth Factor 1 (IGF-1) Modulate Cytoplasmic Glucose and Glycogen Levels but Not Glucose Transport across the Membrane in Astrocytes.

作者信息

Muhič Marko, Vardjan Nina, Chowdhury Helena H, Zorec Robert, Kreft Marko

机构信息

From the Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.

From the Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia, Celica Biomedical, 1000 Ljubljana, Slovenia, and.

出版信息

J Biol Chem. 2015 Apr 24;290(17):11167-76. doi: 10.1074/jbc.M114.629063. Epub 2015 Mar 19.

Abstract

Astrocytes contain glycogen, an energy buffer, which can bridge local short term energy requirements in the brain. Glycogen levels reflect a dynamic equilibrium between glycogen synthesis and glycogenolysis. Many factors that include hormones and neuropeptides, such as insulin and insulin-like growth factor 1 (IGF-1) likely modulate glycogen stores in astrocytes, but detailed mechanisms at the cellular level are sparse. We used a glucose nanosensor based on Förster resonance energy transfer to monitor cytosolic glucose concentration with high temporal resolution and a cytochemical approach to determine glycogen stores in single cells. The results show that after glucose depletion, glycogen stores are replenished. Insulin and IGF-1 boost the process of glycogen formation. Although astrocytes appear to express glucose transporter GLUT4, glucose entry across the astrocyte plasma membrane is not affected by insulin. Stimulation of cells with insulin and IGF-1 decreased cytosolic glucose concentration, likely because of elevated glucose utilization for glycogen synthesis.

摘要

星形胶质细胞含有糖原,这是一种能量缓冲物质,能够满足大脑局部的短期能量需求。糖原水平反映了糖原合成与糖原分解之间的动态平衡。许多因素,包括激素和神经肽,如胰岛素和胰岛素样生长因子1(IGF-1),可能会调节星形胶质细胞中的糖原储备,但细胞水平的详细机制尚不明确。我们使用基于Förster共振能量转移的葡萄糖纳米传感器以高时间分辨率监测胞质葡萄糖浓度,并采用细胞化学方法测定单细胞中的糖原储备。结果表明,葡萄糖耗尽后,糖原储备得以补充。胰岛素和IGF-1促进糖原形成过程。尽管星形胶质细胞似乎表达葡萄糖转运蛋白GLUT4,但胰岛素并不影响葡萄糖跨星形胶质细胞质膜的进入。用胰岛素和IGF-1刺激细胞会降低胞质葡萄糖浓度,这可能是由于糖原合成对葡萄糖的利用增加所致。

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