The release of the adipocytokine visfatin is regulated by glucose and insulin
The release of the adipocytokine visfatin is regulated by glucose and insulin
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DOI：
10.1007/s00125-006-0303-7
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发表时间：
2006-08-01
期刊：
影响因子：
8.2
通讯作者：
Wolzt, M.
中科院分区：
文献类型：
--
作者：
Haider, D. G.;Schaller, G.;Wolzt, M.
新的类似胰岛素的脂肪细胞因子Visfatin被认为与代谢综合征有关，但到目前为止，它的调节还没有被表征。由于Visfatin的胰岛素模拟作用可能是葡萄糖稳态反馈调节的一部分，我们假设Visfatin浓度受到人类血糖或胰岛素水平的影响。在这项随机、双盲、安慰剂对照的交叉研究中，9名健康男性受试者(年龄26岁+/-6岁)参加了三个不同的研究日。每日静脉滴注葡萄糖浓度分别为5.0、8.3和11.1 mmol/L。输注葡萄糖，代表空腹和餐后情况。研究了伴随外源性高胰岛素血症、注射生长抑素抑制内源性胰岛素产生和安慰剂时间控制时Visfatin的血浆浓度。此外，体外培养人脂肪细胞以研究内脂素的释放和基因表达。浓度为8.3和11.1 mmol/L的葡萄糖使循环内脂素从基线浓度的0.5+/-0.0 ng/ml分别增加到0.9+/-0.1和2.1+/-0.3 ng/ml(p<；0.01)。联合应用胰岛素或生长抑素可防止葡萄糖诱导的内脂素升高(p<；0.05)。培养的皮下和内脏脂肪细胞在葡萄糖浓度和时间依赖的刺激下释放等量的内脂素。Visfatin的分泌涉及磷脂酰肌醇3-激酶(PI3-K)和蛋白激酶B(AKT)途径。内脂素的mRNA表达模式与这种蛋白释放的改变是一致的。高血糖会增加循环中的内脂素浓度。外源性高胰岛素血症或生长抑素输注可抑制这种作用。脂肪细胞释放内脂素的葡萄糖信号涉及PI3-激酶/AKT途径。
The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulin-mimetic actions of visfatin may be part of the feedback regulation of glucose homeostasis, we hypothesised that visfatin concentrations are influenced by glucose or insulin blood levels in humans.In this randomised, double-blind, placebo-controlled crossover study, nine healthy male subjects (age 26 +/- 6 years) attended three different study days. On each day, systemic glucose concentrations of 5.0, 8.3 and 11.1 mmol/l were attained by stepwise increases in i.v. infusions of glucose, representing fasting and postprandial conditions. Visfatin plasma concentrations were studied during concomitant exogenous hyperinsulinaemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control. Additionally, human adipocytes were cultured to study visfatin release and mRNA expression in vitro.Glucose concentrations of 8.3 and 11.1 mmol/l increased circulating visfatin from baseline concentrations of 0.5 +/- 0.0 ng/ml to 0.9 +/- 0.1 and 2.1 +/- 0.3 ng/ml, respectively (p < 0.01). Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p < 0.05). Cultured subcutaneous and visceral adipocytes released an equivalent amount of visfatin upon glucose-concentration- and time-dependent stimulation. Visfatin secretion involved the phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase B (AKT) pathways. The mRNA expression pattern of visfatin was consistent with this altered protein release.Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. Glucose signalling for visfatin release in adipocytes involves the PI3-kinase/AKT pathway.