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内脏脂肪素/Nampt/PBEF1 对人脂肪细胞没有直接的胰岛素样作用。

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes.

机构信息

Institut National de la Santé et de la Recherche Médicale (INSERM), U858, Toulouse, France.

出版信息

J Physiol Biochem. 2009 Dec;65(4):351-9. doi: 10.1007/BF03185930.

DOI:10.1007/BF03185930
PMID:20358348
Abstract

Visfatin, a protein identified as a secretion product of visceral fat in humans and mice, is also expressed in different anatomical locations, and is known as pre-B cell-colony enhancing factor (PEBF1). It is also an enzyme displaying nicotinamide phosphoribosyltransferase activity (Nampt). The evidence that levels of visfatin correlate with visceral fat mass has been largely debated and widely extended to other regulations in numerous clinical studies and in diverse animal models. On the opposite, the initial findings regarding the capacity of visfatin/Nampt/PEBF1 to bind and to activate the insulin receptor have been scarcely reproduced, and even were contradicted in recent reports. Since the putative insulin mimicking effects of visfatin/Nampt/PEBF1 have never been tested on mature human adipocytes, at least to our knowledge, we tested different human visfatin batches on human fat cells freshly isolated from subcutaneous abdominal fat and exhibiting high insulin responsiveness. Up to 10 nM, visfatin was devoid of clear activatory action on glucose transport in human fat cells while, in the same conditions, insulin increased by more than threefold the basal 2-deoxyglucose uptake. Moreover, visfatin was unable to mimic the lipolysis inhibition induced by insulin. Visfatin definitively cannot be considered as a direct activator of insulin signalling in human fat cells. Nevertheless itsin vivo effects on insulin release and on glucose handling deserve to further study the role of this multifunctional extracellular enzyme in obese and diabetic states.

摘要

内脏脂肪组织在人类和小鼠中被鉴定为一种分泌产物的内脏脂肪素(Visfatin),也在不同的解剖部位表达,并被称为前 B 细胞集落增强因子(PEBF1)。它也是一种具有烟酰胺磷酸核糖基转移酶活性(Nampt)的酶。内脏脂肪素水平与内脏脂肪量相关的证据存在很大争议,并在大量临床研究和不同动物模型中广泛扩展到其他调节作用。相反,关于内脏脂肪素/Nampt/PEBF1 结合和激活胰岛素受体的能力的最初发现,很少被复制,甚至在最近的报告中被反驳。由于尚未在成熟的人类脂肪细胞上测试内脏脂肪素/Nampt/PEBF1 的假定胰岛素模拟作用,至少据我们所知,我们在从腹部皮下脂肪新鲜分离的、对胰岛素反应性高的人类脂肪细胞上测试了不同的人类内脏脂肪素批次。在 10 nM 时,内脏脂肪素对人类脂肪细胞的葡萄糖转运没有明显的激活作用,而在相同条件下,胰岛素使基础 2-脱氧葡萄糖摄取增加了三倍以上。此外,内脏脂肪素不能模拟胰岛素诱导的脂肪分解抑制。内脏脂肪素不能被认为是人类脂肪细胞中胰岛素信号的直接激活剂。然而,其在体内对胰岛素释放和葡萄糖处理的影响值得进一步研究这种多功能细胞外酶在肥胖和糖尿病状态下的作用。

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