Andreozzi Francesco, Mannino Gaia Chiara, Mancuso Elettra, Spiga Rosangela, Perticone Francesco, Sesti Giorgio
Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Catanzaro (CZ), Italy.
PLoS One. 2017 Jun 21;12(6):e0179834. doi: 10.1371/journal.pone.0179834. eCollection 2017.
To evaluate if plasma kisspeptin concentrations are associated with insulin secretion, as suggested by recent in vitro studies, independently of confounders. 261 nondiabetic subjects were stratified into tertiles according to kisspeptin values. Insulin secretion was assessed using indexes derived from oral glucose tolerance test (OGTT). After adjusting for age, gender, and BMI, subjects in the highest (tertile 3) kisspeptin group exhibited significantly lower values of insulinogenic index, corrected insulin response (CIR30), and Stumvoll indexes for first-phase and second-phase insulin release as compared with low (tertile 1) or intermediate (tertile 2) kisspeptin groups. Univariate correlations between kisspeptin concentration and metabolic variables showed that kisspeptin concentration was significantly and positively correlated with age, blood pressure, and 2-h post-load glucose, and inversely correlated with BMI, and waist circumference. There was an inverse relationship between kisspeptin levels and OGTT-derived indexes of glucose-stimulated insulin secretion. A multivariable regression analysis in a model including all the variables significantly correlated with kisspeptin concentration showed thar age (β = -0.338, P<0.0001), BMI (β = 0.272, P<0.0001), 2-h post-load glucose (β = -0.229, P<0.0001), and kisspeptin (β = -0.105, P = 0.03) remained associated with insulinogenic index. These factors explained 34.6% of the variance of the insulinogenic index. In conclusion, kisspeptin concentrations are associated with insulin secretion independently of important determinants of glucose homeostasis such as gender, age, adiposity, 2-h post-load glucose, and insulin sensitivity.
为了评估血浆 kisspeptin 浓度是否如近期体外研究所示，独立于混杂因素与胰岛素分泌相关。根据 kisspeptin 值将 261 名非糖尿病受试者分层为三分位数。使用口服葡萄糖耐量试验（OGTT）得出的指标评估胰岛素分泌。在调整年龄、性别和体重指数（BMI）后，与低（三分位数 1）或中（三分位数 2）kisspeptin 组相比，最高（三分位数 3）kisspeptin 组的受试者胰岛素生成指数、校正胰岛素反应（CIR30）以及第一相和第二相胰岛素释放的 Stumvoll 指数值显著更低。kisspeptin 浓度与代谢变量之间的单变量相关性表明，kisspeptin 浓度与年龄、血压和负荷后 2 小时血糖显著正相关，与 BMI 和腰围呈负相关。kisspeptin 水平与 OGTT 衍生的葡萄糖刺激胰岛素分泌指标之间存在负相关关系。在一个包含所有与 kisspeptin 浓度显著相关变量的模型中进行多变量回归分析显示，年龄（β = -0.338，P<0.0001）、BMI（β = 0.272，P<0.0001）、负荷后 2 小时血糖（β = -0.229，P<0.0001）和 kisspeptin（β = -0.105，P = 0.03）仍与胰岛素生成指数相关。这些因素解释了胰岛素生成指数 34.6%的变异。总之，kisspeptin 浓度与胰岛素分泌相关，独立于葡萄糖稳态的重要决定因素，如性别、年龄、肥胖、负荷后 2 小时血糖和胰岛素敏感性。
