Increased SRF Transcriptional Activity is a Novel Signature of Insulin Resistance in Humans and Mice

ABSTRACT: Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) and is even present in offspring of diabetic parents. However, molecular mediators of insulin resistance remain unclear. We find that the top-ranking gene set in expression analysis of muscle from humans with T2D and normoglycemic insulin resistant subjects with parental family history (FH+) of T2D is increased expression of actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator MKL1. Furthermore, the SRF activator STARS is upregulated in FH+ and T2D and inversely correlated with insulin sensitivity. These patterns are recapitulated in insulin resistant mice, and linked to alterations in two other regulators of this pathway: reduced G-actin and increased nuclear loc

ORGANISM(S): Homo sapiens

SUBMITTER: Mary Elizabeth Patti 

PROVIDER: E-GEOD-25462 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress