Abstract
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. Design: 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. Results: 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. Conclusions: 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.
Highlights
The number of individuals diagnosed with type-2 diabetes mellitus (T2D) has continued to increase over the past several decades [1]
Given the current understanding of the relationships between T2D, growth hormone (GH), insulin-like growth factor-1 (IGF-1), coupled with the lack of exercise-related studies in the area of gene expression, this study aimed to investigate the effects of an acute bout of moderate-intensity exercise on peripheral blood mononuclear cells (PBMC) gene expression between healthy and PD individuals
While no differences in IL-6 (IL6) messenger ribonucleic acid (mRNA) were observed between groups or across time, a significant group difference was observed for IL6 receptor (IL6R) variant 1 (p = 0.010); indicating elevated expression of IL6R mRNA in the PD group compared to CON
Summary
The number of individuals diagnosed with type-2 diabetes mellitus (T2D) has continued to increase over the past several decades [1]. The complications associated with T2D include higher risk of heart attack, stroke, kidney disease, and increased rates of hospitalization, as well as premature death [2]. There is significant inter-individual variation in disease progression that occurs over time and impacts different systems across levels of physiological organization. It should be remembered that lower levels of physiological organization (i.e. gene expression) work on faster timescales and are more flexible than markers at higher levels of organization (i.e. proteins). This physiological organization contextualizes how changes and adaptations at the gene expression level may be more similar between PD and T2D, whereas time-corresponding protein levels may be more similar between PD and CON. Since disease progression occurs on a continuum, understanding how physiological responses at various levels of biological organization differ throughout the disease continuum may provide important information for future methods of detection and treatment
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