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Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

ABSTRACT: This study, using a growth hormone (GH)-deficient dwarf animal model and peripheral GH replacement, investigated the effects of circulating IGF-1 during adolescence on IGF-1 levels in the brain. Our results demonstrated that hippocampal IGF-1 protein concentrations during adolescence are highly regulated by circulating IGF-1, which were reduced by GH deficiency and restored by systematic GH replacement. In contrast, IGF-1 levels in the CSF were decreased by GH deficiency but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF-1 levels did not modify the transcription of IGF-1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE29512 | GEO | 2011/07/21

SECONDARY ACCESSION(S): PRJNA141463

REPOSITORIES: GEO

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Project description: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 beadchip arrays that were scanned and analyzed by a gene expression module. 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), ∆GH (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.

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Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

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