Berry Nathaniel T, Hubal Monica, Wideman Laurie
University of North Carolina at Greensboro, Greensboro, NC, United States of America.
George Washington University Milken Institute School of Public Health, Washington, D.C., United States of America.
PLoS One. 2018 Jan 19;13(1):e0191331. doi: 10.1371/journal.pone.0191331. eCollection 2018.
The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a worldwide epidemic. African American (AA) individuals are disproportionately more likely to become diabetic than other ethnic groups. Over the long-term, metabolic complications related to diabetes result in significant alterations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited exercise-related studies in the area of gene expression changes with disease progression, the objective of this study was to examine differences in exercise-induced gene expression related to the GH and IGF-1 pathways in peripheral blood mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals.
Ten subjects [5 PD (age = 35±9.3 yr, BMI = 32.1±4.0, FBG = 101.8±1.3 mg/dl) and 5 CON (age = 31±9.4 yr, BMI = 29.4±5.2, FBG = 82.8±9.7 mg/dl)] had blood drawn for RNA isolation prior to exercise (Pre), immediately following acute moderate intensity exercise on a treadmill (Post-1), 6-hours post (Post-6), and 24-hours post (Post-24). Isolation of mRNA from PBMCs was performed using ficoll separation, while the profiling of mRNA expression was performed using Illumina beadchip arrays with standard protocols. Scan results were statistically analyzed for a specific list of genes related to GH and IGF-1. GH and IGF-1 protein levels were also assessed in each sample. To address issues of normality, all GH and IGF-1 data were log-transformed prior to analysis. Statistical significance was set at p<0.05.
Group differences for GH2 variant 2 (p = 0.070) and GH2 variant 3 (p = 0.059) were coupled with significant alterations in IGF-1 mRNA over time (p = 0.024). A significant interaction between group and time was observed for GHRH mRNA (p = 0.008). No group differences were observed in GH AUC (p = 0.649), ΔGH (p = 0.331), GHrec (p = 0.294), or IGF-1 AUC (p = 0.865), representing a similar exercise-induced GH and IGF-1 response for both groups.
Analysis of GH and IGF-1 related-gene expression indicates that mild elevations in fasting blood glucose and exercise-induced alterations in gene expression are impacted by the prediabetic state.
糖尿病前期(PD)和2型糖尿病(T2D)的发病率在全球范围内呈流行趋势。非裔美国人(AA)比其他种族更容易患糖尿病。从长期来看,与糖尿病相关的代谢并发症会导致生长激素(GH)和胰岛素样生长因子-1(IGF-1)发生显著变化。鉴于在疾病进展过程中基因表达变化领域与运动相关的研究有限,本研究的目的是检查健康(CON)和糖尿病前期AA个体外周血单核细胞(PBMC)中与GH和IGF-1途径相关的运动诱导基因表达差异。
10名受试者[5名糖尿病前期患者(年龄=35±9.3岁,体重指数=32.1±4.0,空腹血糖=101.8±1.3mg/dl)和5名健康对照者(年龄=31±9.4岁,体重指数=29.4±5.2,空腹血糖=82.8±9.7mg/dl)]在运动前(Pre)、在跑步机上进行急性中等强度运动后立即(Post-1)、运动后6小时(Post-6)和运动后24小时(Post-24)采集血液用于RNA分离。使用菲可分离法从PBMC中分离mRNA,同时使用Illumina beadchip阵列按照标准方案对mRNA表达进行分析。对与GH和IGF-1相关的特定基因列表的扫描结果进行统计分析。还评估了每个样本中的GH和IGF-1蛋白水平。为了解决正态性问题,所有GH和IGF-1数据在分析前进行对数转换。统计学显著性设定为p<0.05。
GH2变体2(p=0.070)和GH2变体3(p=0.059)的组间差异与IGF-1 mRNA随时间的显著变化相关(p=0.024)。观察到生长激素释放激素(GHRH)mRNA在组和时间之间存在显著交互作用(p=0.008)。在GH曲线下面积(p=0.649)、ΔGH(p=0.331)、GHrec(p=0.294)或IGF-1曲线下面积(p=0.865)方面未观察到组间差异,这表明两组的运动诱导GH和IGF-1反应相似。
对GH和IGF-1相关基因表达的分析表明,空腹血糖轻度升高和运动诱导的基因表达变化受糖尿病前期状态影响。