Ma Elizabeth, Fu Yuchang, Garvey W Timothy
1 Department of Nutrition Sciences, University of Alabama at Birmingham , Birmingham, Alabama.
2 The Birmingham Veterans Affairs Medical Center , Birmingham, Alabama.
Metab Syndr Relat Disord. 2018 Mar;16(2):82-89. doi: 10.1089/met.2017.0101. Epub 2018 Jan 23.
Insulin resistance disrupts metabolic processes and leads to various chronic disease states such as diabetes and metabolic syndrome (MetS). However, the mechanism linking insulin resistance with cardiometabolic disease pathophysiology is still unclear. One possibility may be through circulating microRNAs (c-miRs), which can alter gene expression in target tissues. Our goal was to assess the relationship of c-miRs with insulin sensitivity, as measured by the gold standard, hyperinsulinemic-euglycemic clamp technique.
Eighty-one nondiabetic, sedentary, and weight-stable patients across a wide range of insulin sensitivities were studied. Measurements were taken for blood pressure, anthropometric data, fasting glucose and lipids, and insulin sensitivity measured by clamp. After an initial screening array to identify candidate miRs in plasma, all samples were assessed for relationships between these c-miRs and insulin sensitivity, as well as associated metabolic factors.
miR-16 and miR-107 were positively associated with insulin sensitivity (R = 0.09, P = 0.0074 and R = 0.08, P = 0.0417, respectively) and remained so after adjustment with body mass index (BMI). After adjusting for BMI, miR-33, -150, and -222 were additionally found to be related to insulin sensitivity. Regarding metabolic risk factors, miR-16 was associated with waist circumference (r = -0.25), triglycerides (r = -0.28), and high-density lipoprotein (r = 0.22), while miR-33 was inversely associated with systolic blood pressure (r = -0.29). No significant relationships were found between any candidate c-miRs and BMI, diastolic blood pressure, or fasting glucose.
Our results show that relative levels of circulating miR-16, -107, -33, -150, and -222 are associated with insulin sensitivity and metabolic risk factors, and suggest that multiple miRs may act in concert to produce insulin resistance and the clustering of associated traits that comprise the MetS. Therefore, miRs may have potential as novel therapeutic targets or agents in cardiometabolic disease.
胰岛素抵抗会扰乱代谢过程，并导致多种慢性疾病状态，如糖尿病和代谢综合征（MetS）。然而，将胰岛素抵抗与心脏代谢疾病病理生理学联系起来的机制仍不清楚。一种可能性可能是通过循环微RNA（c-miRs），其可改变靶组织中的基因表达。我们的目标是评估c-miRs与胰岛素敏感性之间的关系，胰岛素敏感性通过金标准高胰岛素-正常血糖钳夹技术进行测量。
研究了81例非糖尿病、久坐且体重稳定的患者，其胰岛素敏感性范围广泛。测量了血压、人体测量数据、空腹血糖和血脂，并通过钳夹测量胰岛素敏感性。在进行初步筛选阵列以鉴定血浆中的候选miRs后，评估所有样本中这些c-miRs与胰岛素敏感性以及相关代谢因子之间的关系。
miR-16和miR-107与胰岛素敏感性呈正相关（分别为R = 0.09，P = 0.0074和R = 0.08，P = 0.0417），在根据体重指数（BMI）进行调整后依然如此。在调整BMI后，还发现miR-33、-150和-222与胰岛素敏感性有关。关于代谢危险因素，miR-16与腰围（r = -0.25）、甘油三酯（r = -0.28）和高密度脂蛋白（r = 0.22）相关，而miR-33与收缩压呈负相关（r = -0.29）。未发现任何候选c-miRs与BMI、舒张压或空腹血糖之间存在显著关系。
我们的结果表明，循环miR-16、-107、-33、-150和-222的相对水平与胰岛素敏感性和代谢危险因素相关，并提示多种miRs可能共同作用以产生胰岛素抵抗以及构成MetS的相关特征的聚集。因此，miRs可能具有作为心脏代谢疾病新型治疗靶点或药物的潜力。
