可溶性表皮生长因子受体（一种肝源性激素）和脂联素（一种脂肪因子）是与2型糖尿病患者胰岛素抵抗不同方面相关的生物标志物。
Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects.
作者信息
Kyohara Mayu, Shirakawa Jun, Okuyama Tomoko, Togashi Yu, Inoue Ryota, Li Jinghe, Miyashita Daisuke, Terauchi Yasuo
机构信息
Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama-City University, 3-9 Fukuura, Yokohama, 236-0004 Japan.
Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, 3-39-15 Showa-machi, Maebashi, 371-8512 Japan.
出版信息
Diabetol Metab Syndr. 2020 Sep 29;12:83. doi: 10.1186/s13098-020-00591-7. eCollection 2020.
BACKGROUND
Insulin resistance can occur in all metabolic organs including the liver, adipose tissue, and skeletal muscles. Circulating soluble epidermal growth factor receptor (soluble EGFR) and adipsin levels are altered in obese diabetic mice and are possibly correlated with insulin resistance in both mice and humans. Here, we investigated the significance of soluble EGFR and adipsin as biomarkers for insulin resistance in Japanese subjects with type 2 diabetes.
METHODS
We measured the soluble EGFR and adipsin levels in sera from 47 non-diabetic subjects and 106 subjects with type 2 diabetes using enzyme-linked immunosorbent assays (ELISAs) and analyzed the correlations between the soluble EGFR or adipsin levels and metabolic parameters in type 2 diabetes subjects. We also measured the gene expression levels of and (adipsin) in the liver, adipose tissue, and skeletal muscle in mice with/without obesity or diabetes.
RESULTS
The soluble EGFR levels were correlated with the fasting blood glucose level ( = 0.010), HOMA-IR ( = 0.035), HbA1c level ( = 0.007), HDL-cholesterol level ( = 0.044), and FIB-4 index ( = 0.017) after adjustments for age, sex, and total cholesterol levels. These factors are known to be related to hepatic insulin resistance. The serum adipsin levels were correlated with BMI ( < 0.001), waist circumference ( < 0.001), fasting serum insulin level ( = 0.001), HOMA-IR ( = 0.009), CPR-index ( = 0.045), and FIB-4 index ( = 0.007) after adjustments for age, sex and eGFR levels. Abdominal adiposity leads to the potentiation of these factors. The expression of was abundant in the liver, while was predominantly expressed in adipose tissue in mice.
CONCLUSIONS
Soluble EGFR, a hepatokine, is correlated with insulin resistance in the liver, while adipsin, an adipokine, is associated with adipose insulin resistance.Trial registration: UMIN Clinical Trials Registry (www.umin.ac.jp), UMIN000020474. Registered 8 January 2016.
背景
胰岛素抵抗可发生于包括肝脏、脂肪组织和骨骼肌在内的所有代谢器官。肥胖糖尿病小鼠循环中的可溶性表皮生长因子受体（可溶性EGFR）和脂联素水平发生改变，且可能与小鼠和人类的胰岛素抵抗相关。在此，我们研究了可溶性EGFR和脂联素作为日本2型糖尿病患者胰岛素抵抗生物标志物的意义。
方法
我们使用酶联免疫吸附测定法（ELISA）测量了47名非糖尿病受试者和106名2型糖尿病受试者血清中的可溶性EGFR和脂联素水平，并分析了2型糖尿病受试者中可溶性EGFR或脂联素水平与代谢参数之间的相关性。我们还测量了有/无肥胖或糖尿病的小鼠肝脏、脂肪组织和骨骼肌中 和 （脂联素）的基因表达水平。
结果
在对年龄、性别和总胆固醇水平进行校正后，可溶性EGFR水平与空腹血糖水平（ = 0.010）、稳态模型评估的胰岛素抵抗指数（HOMA-IR， = 0.035）、糖化血红蛋白水平（ = 0.007）、高密度脂蛋白胆固醇水平（ = 0.044）以及FIB-4指数（ = 0.017）相关。这些因素已知与肝脏胰岛素抵抗有关。在对年龄、性别和估算肾小球滤过率（eGFR）水平进行校正后，血清脂联素水平与体重指数（BMI， < 0.001）、腰围（ < 0.001）、空腹血清胰岛素水平（ = 0.001）、HOMA-IR（ = 0.009）、CPR指数（ = 0.045）以及FIB-4指数（ = 0.007）相关。腹部肥胖会增强这些因素。 在肝脏中表达丰富，而 在小鼠脂肪组织中主要表达。
结论
可溶性EGFR作为一种肝源细胞因子，与肝脏胰岛素抵抗相关，而脂联素作为一种脂肪细胞因子，与脂肪组织胰岛素抵抗相关。试验注册：UMIN临床试验注册中心（www.umin.ac.jp），UMIN000020474。于2016年1月8日注册。
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