Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
J Clin Endocrinol Metab. 2013 Jan;98(1):290-8. doi: 10.1210/jc.2012-2466. Epub 2012 Nov 26.
Secreted frizzled-related protein-5 (Sfrp5) is a novel adipocyte-secreted hormone that has been shown to link obesity with diabetes. Studies in mice have revealed that Sfrp5 represents a potential target for the control of obesity-linked abnormalities in glucose homeostasis.
Our objective was to gain insight into the physiological role of circulating Sfrp5 in humans.
We conducted a series of cross-sectional and interventional studies of the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Subjects included 104 healthy subjects, 101 with impaired glucose tolerance, and 112 with newly diagnosed type 2 diabetes mellitus and, in a separate study, 30 healthy women, and 32 women with polycystic ovarian syndrome (PCOS). Oral glucose tolerance test and euglycemic-hyperinsulinemic clamp were performed to assess glucose tolerance and insulin sensitivity.
Circulating Sfrp5 was significantly lower in both impaired glucose intolerance and newly diagnosed type 2 diabetes mellitus than in individuals with normal glucose tolerance (P < 0.01). Overweight/obese subjects had significantly lower Sfrp5 levels than lean individuals (P < 0.01), but females had higher Sfrp5 levels than males (P < 0.05). In a separate study, Sfrp5 levels were lower in PCOS women than healthy women (P < 0.05). Moreover, circulating Sfrp5 correlated with markers of adiposity, including body mass index, waist-to-hip ratio, percent body fat, homeostasis model assessment of insulin resistance, lipid profile, and adiponectin. Hyperglycemia decreased circulating Sfrp5 levels, whereas liraglutide increased Sfrp5 levels. In the euglycemic-hyperinsulinemic state, circulating Sfrp5 was significantly decreased in healthy women but not in PCOS women.
We conclude that circulating Sfrp5 is likely to play a major role in insulin resistance in humans.
分泌卷曲相关蛋白 5（Sfrp5）是一种新型脂肪细胞分泌的激素，已被证明将肥胖与糖尿病联系起来。在小鼠中的研究表明，Sfrp5 代表了控制肥胖相关葡萄糖稳态异常的潜在靶点。
我们旨在深入了解循环 Sfrp5 在人体中的生理作用。
我们对中国重庆医科大学第二附属医院内科的普通人群和门诊患者进行了一系列横断面和干预研究。研究对象包括 104 名健康受试者、101 名糖耐量受损者和 112 名新诊断的 2 型糖尿病患者，以及在另一项研究中，30 名健康女性和 32 名多囊卵巢综合征（PCOS）女性。进行口服葡萄糖耐量试验和正常血糖高胰岛素钳夹试验以评估葡萄糖耐量和胰岛素敏感性。
在糖耐量受损和新诊断的 2 型糖尿病患者中，循环 Sfrp5 均明显低于葡萄糖耐量正常者（P < 0.01）。超重/肥胖者的 Sfrp5 水平明显低于瘦者（P < 0.01），但女性的 Sfrp5 水平高于男性（P < 0.05）。在另一项研究中，PCOS 女性的 Sfrp5 水平低于健康女性（P < 0.05）。此外，循环 Sfrp5 与肥胖标志物相关，包括体重指数、腰臀比、体脂百分比、胰岛素抵抗评估的稳态模型、血脂谱和脂联素。高血糖降低了循环 Sfrp5 水平，而利拉鲁肽增加了 Sfrp5 水平。在正常血糖高胰岛素状态下，健康女性的循环 Sfrp5 水平明显降低，但 PCOS 女性则不然。
我们得出结论，循环 Sfrp5 可能在人类胰岛素抵抗中起主要作用。
