内科学
内分泌学
连环素
下丘脑
生物
Wnt信号通路
连环蛋白
信号转导
磷酸化
粘合连接
葡萄糖稳态
细胞生物学
胰岛素
钙粘蛋白
细胞
胰岛素抵抗
生物化学
医学
作者
Hayden John Leonard McEwen,Emmanuelle Cognard,Sharon R Ladyman,Zin Khant Aung,Alexander Tups,Peter R. Shepherd,David R. Grattan
摘要
β‐catenin is a multifunctional protein that not only acts in the canonical Wnt/β‐catenin pathway to regulate gene expression but also binds to cadherin proteins in adherens junctions, where it plays a key role in regulating cytoskeleton linked with these junctions. Recently, evidence has been presented indicating an essential role for β‐catenin in regulating the trafficking of insulin vesicles in β‐cells and showing that changes in nutrient levels rapidly alter levels of β‐catenin in these cells. Given the importance of neuroendocrine hormone secretion in the regulation of whole body glucose homeostasis, the present study aimed to investigate whether β‐catenin signalling is regulated in the hypothalamus during the normal physiological response to food intake. Rats were subjected to a fasting/re‐feeding paradigm, and then samples were collected at specific timepoints for analysis of β‐catenin expression by immunohistochemistry and western blotting. Changes in gene expression were assessed by a quantitative reverse transcriptase‐polymerase chain reaction. Using immunohistochemistry, feeding acutely increased detectable cytoplasmic levels of β‐catenin (‘stabilised β‐catenin’) in neurones in specific regions of the hypothalamus involved in metabolic regulation, including the arcuate, dorsomedial and paraventricular nuclei of the hypothalamus. Feeding‐induced elevations in β‐catenin in these nuclei were associated with an increased transcription of several genes known to be responsive to Wnt/β‐catenin signalling. The effect of feeding was mimicked by administration of the GLP‐1 agonist exendin‐4 and was also characterised by cAMP‐dependent phosphorylation of β‐catenin at serine residues 552 and 675. These data suggest that β‐catenin/T cell factor signalling is involved in metabolic sensing in the hypothalamus.
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