Department of Internal Medicine I, University Medical Center, D-93042 Regensburg, Germany.
J Clin Endocrinol Metab. 2011 Aug;96(8):2493-501. doi: 10.1210/jc.2011-0342. Epub 2011 Jun 15.
Visfatin represents an adipokine of the visceral adipose tissue exerting pleiotropic effects. The aim of the study was to characterize the physiological regulation of visfatin release in vivo in healthy, nondiabetic probands and in adipocytes in vitro.
One hundred healthy subjects (64 females and 36 males) underwent an oral glucose tolerance test (75 g). Probands were characterized by anthropometric and laboratory parameters. Fasting and postprandial (1 and 2 h) serum concentrations of glucose, insulin, and visfatin were measured. Stimulation experiments using glucose, insulin, mannitol, and glucagon-like peptide-1 (GLP-1) were performed on 3T3-L1 adipocytes including Western blot analysis.
Fasting visfatin levels were not different between males/females or lean/obese individuals but were negatively (r = -0.5; P < 0.001) correlated with fasting glucose levels. Visfatin levels were rapidly and significantly suppressed (P < 0.001) upon an oral glucose intake, and this suppression was more pronounced in overweight and female probands. In vitro experiments demonstrated that hyperglycemia, osmotic stress, and sex steroids did not influence visfatin release. In contrast, insulin strongly (P = 0.002) inhibited visfatin release in vitro by approximately 50%, and this suppression was more pronounced under hyperglycemia. Importantly, GLP-1 strongly (P < 0.001) inhibited adipocytic visfatin release by approximately 50%.
Insulin and GLP-1 are responsible for the rapid suppression of visfatin levels upon an oral glucose uptake in healthy probands. The inhibitory effect of GLP-1 on adipocytic visfatin release together with the absence of direct glucose effects on visfatin release suggests the existence of a novel incretin-like effect represented by a GLP-1/visfatin/axis.
脂联素是内脏脂肪组织的一种脂肪因子，具有多种作用。本研究旨在描述健康、非糖尿病个体体内和体外脂肪细胞中脂联素分泌的生理调节。
100 名健康受试者（64 名女性和 36 名男性）接受口服葡萄糖耐量试验（75 g）。通过人体测量和实验室参数对受试者进行特征描述。测量空腹和餐后（1 和 2 h）血清葡萄糖、胰岛素和脂联素浓度。对 3T3-L1 脂肪细胞进行葡萄糖、胰岛素、甘露醇和胰高血糖素样肽-1（GLP-1）刺激实验，包括 Western blot 分析。
空腹脂联素水平在男性/女性或瘦/肥胖个体之间无差异，但与空腹血糖水平呈负相关（r = -0.5；P < 0.001）。口服葡萄糖摄入后，脂联素水平迅速且显著降低（P < 0.001），超重和女性受试者的抑制作用更为明显。体外实验表明，高血糖、渗透应激和性激素不会影响脂联素的释放。相反，胰岛素强烈（P = 0.002）抑制体外脂联素的释放，约 50%，在高血糖下抑制作用更为明显。重要的是，GLP-1 强烈（P < 0.001）抑制脂肪细胞脂联素的释放，约 50%。
胰岛素和 GLP-1 负责健康个体口服葡萄糖摄入后脂联素水平的快速抑制。GLP-1 对脂肪细胞脂联素释放的抑制作用以及葡萄糖对脂联素释放的直接作用缺失提示存在一种新型的肠促胰岛素样作用，由 GLP-1/脂联素/轴代表。
