Project description:The goal of the current study was to examine the extent to which TGF-beta signaling contributes to insulin-induced transcriptional responses in endothelial cells (HUVECs). HUVECs cells were treated with or without insulin in the absence or presence of SB431542, a TGF-beta receptor kinase inhibitor. Cells were sequenced using Hiseq 2000 (Illumina) as paired-end 2x100 base reads.
Project description:Genome wide DNA methylation profiling of monocytes from insulin sensitive and insulin resistant HIV-infected patients. The Illumina Infinium Human Methylation 450k Beadchip was used to obtain DNA methylation profiling across 450,000+ CpGs. Samples included monocytes from 37 HIV-infected individuals, of which 14 were insulin resistant and 23 were insulin sensitive, monocytes from 9 HIV-seronegative individuals, of which 4 were insulin sensitive and 5 insulin resistant, and FACS monocyte subsets (classical, intermediate, and non-classical monocytes) from two healthy donors.
Project description:Objective: To study if diabetic and insulin-resistant states lead to mitochondrial dysfunction in the liver, or alternatively, if there is adaption of mitochondrial function to these states in the long-term range. Results: High-fat diet (HFD) caused insulin resistance and severe hepatic lipid accumulation, but respiratory chain parameters were unchanged. Livers from insulin-resistant IR/IRS-1+/- mice had normal lipid contents and normal respiratory chain parameters, however showed mitochondrial uncoupling. Livers from severely hyperglycemic and hypoinsulimic, streptozotocin (STZ)-treated mice had massively depleted lipid levels, but respiratory chain abundance was unchanged. However, their mitochondria showed increased abundance and activity of the respiratory chain, which was better coupled compared to controls. Conclusions: Insulin resistance, either induced by obesity or by genetic manipulation, does not cause mitochondrial dysfunction in the liver of mice. However, severe insulin deficiency and high blood glucose levels in mice cause an enhanced performance of the respiratory chain, probably in order to maintain the high energy requirement of the unsuppressed gluconeogenesis. We performed gene expression microarray analysis on liver tissue derived from mice treated with STZ or standard diet (control).