Regulation of insulin secretion, glucokinase gene transcription and beta cell proliferation by adipocyte-derived Wnt signalling molecules

Regulation of insulin secretion, glucokinase gene transcription and beta cell proliferation by adipocyte-derived Wnt signalling molecules
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DOI:
10.1007/s00125-007-0848-0
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发表时间:
2008-01-01
期刊:
影响因子:
8.2
通讯作者:
Scherbaum, W. A.
Scherbaum, W. A.
中科院分区:
医学1区
文献类型:
--
作者:
Schinner, S.;Uelgen, F.;Scherbaum, W. A.

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目的/假设脂肪细胞分泌信号分子,引起靶细胞,包括胰腺β细胞的反应。Wnt信号分子最近被鉴定为新的脂肪细胞衍生因子。它们还调节胰腺β细胞中的胰岛素分泌和细胞周期。本研究旨在探讨脂肪细胞来源的Wnt信号分子对胰岛素分泌和β细胞增殖的影响。方法分离人脂肪细胞,制备脂肪细胞条件培养基(Fatcell-conditionedmedium,FCCM)。用FCCM刺激Ins-1细胞,并用报告基因瞬时转染。在Ins-1细胞和原代胰岛细胞中使用[H-3]胸苷掺入进行增殖测定。用放射免疫法测定原代胰岛的胰岛素分泌。结果用人FCCM处理的Ins-1细胞中T细胞特异性转录因子报告基因(TOPFLASH)的转录增加(241%,p < 0.05),而用人FCCM处理的Ins-1细胞中T细胞特异性转录因子报告基因(TOPFLASH)的转录增加(241%,p < 0.05)。
Aims/hypothesis Adipocytes secrete signalling molecules that elicit responses from target cells, including pancreatic beta cells. Wnt signalling molecules have recently been identified as novel adipocyte-derived factors. They also regulate insulin secretion in pancreatic beta cells and the cell cycle. The aim of this study was to investigate the effect of adipocyte-derived Wnt signalling molecules on insulin secretion and beta cell proliferation.Methods Human adipocytes were isolated to generate fat cell-conditioned medium (FCCM). Ins-1 cells were stimulated with FCCM and transiently transfected with reporter genes. Proliferation assays using [H-3]thymidine incorporation were carried out in Ins-1 cells and primary islet cells. Insulin secretion from primary islets was assessed by radioimmunoassay. Gene expression in primary islets was assessed by Taqman PCR.Results Treatment with human FCCM increased the transcription of a T cell-specific transcription factor reporter gene (TOPFLASH) in Ins-1 cells (241%, p