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Insulin receptor associates with promoters genome-wide and regulates gene expression [ChIP-seq]

ABSTRACT: ChIP-seq analysis demonstrates an association of insulin receptor (IR) and RNA polymerase II on chromatin, with striking enrichment at gene promoters.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107335 | GEO | 2019/04/04

REPOSITORIES: GEO

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Insulin receptor associates with promoters genome-wide and regulates gene expression [RNA-seq]

Project description:RNA-seq analysis identifies transcripts regulated by insulin treatment.

2019-04-04 | GSE107334 | GEO

Rescue of insulin receptor condensates in insulin resistant cells

Project description:Insulin resistance is accompanied by chronic hyperinsulinemia and is associated with type 2 diabetes and other metabolic syndromes in a substantial portion of the population. The risk factors and features of insulin resistance have been thoroughly described but its mechanistic triggers are still under study. Here we consider a condensate model for insulin receptor (IR) function in normal conditions and when dysregulated in chronic hyperinsulinemia-induced insulin resistance. We find that IR is incorporated into liquid-like condensates at the plasma membrane, in the cytoplasm and in the nucleus of liver cells, and provide evidence for insulin-dependent IR function in condensates. Insulin stimulation promotes further incorporation of IR into these dynamic condensates in insulin sensitive cells, which form and dissolve on short, sub-minute time-scales. In contrast, insulin stimulation does not promote further incorporation of IR into condensates in insulin resistant cells, where IR molecules within condensates exhibit less dynamic behavior. Metformin treatment of insulin resistant cells rescues IR condensate dynamics and insulin responsiveness. Insulin resistant cells experience high levels of oxidative stress, which causes reduced condensate dynamics, and treatment of these cells with metformin reduces ROS levels and returns condensates to their normal dynamic behavior. The condensate model we propose can account for features of normal and dysregulated insulin response and has implications for improved therapeutic approaches to insulin resistance.

2023-07-28 | GSE181096 | GEO

Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression.

Project description:Insulin receptor (IR) signaling is central to normal metabolic control and dysregulated in prevalent chronic diseases. IR binds insulin at the cell surface and transduces rapid signaling via cytoplasmic kinases. However, mechanisms mediating long-term effects of insulin remain unclear. Here, we show that IR associates with RNA polymerase II in the nucleus, with striking enrichment at promoters genome-wide. The target genes were highly enriched for insulin-related functions including lipid metabolism and protein synthesis and diseases including diabetes, neurodegeneration, and cancer. IR chromatin binding was increased by insulin and impaired in an insulin-resistant disease model. Promoter binding by IR was mediated by coregulator host cell factor-1 (HCF-1) and transcription factors, revealing an HCF-1-dependent pathway for gene regulation by insulin. These results show that IR interacts with transcriptional machinery at promoters and identify a pathway regulating genes linked to insulin's effects in physiology and disease.

| S-EPMC6478446 | biostudies-literature

Insulin receptor associates with promoters genome-wide and regulates gene expression

Project description:Insulin receptor associates with promoters genome-wide and regulates gene expression

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Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

Project description:Global energy balance in mammals is controlled by the actions of circulating hormones that coordinate fuel production and utilization in metabolically active tissues. Bone-derived osteocalcin, in its undercarboxylated, hormonal form, regulates fat deposition and is a potent insulin secretagogue. Here, we show that insulin receptor (IR) signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the Runx2 inhibitor Twist-2. Mice lacking IR in osteoblasts have low circulating undercarboxylated osteocalcin and reduced bone acquisition due to decreased bone formation and deficient numbers of osteoblasts. With age, these mice develop marked peripheral adiposity and hyperglycemia accompanied by severe glucose intolerance and insulin resistance. The metabolic abnormalities in these mice are improved by infusion of exogenous under-carboxylated osteocalcin. These results indicate the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast ensures osteoblast differentiation and stimulates osteocalcin production, which in turn regulates insulin sensitivity and pancreatic insulin secretion to control glucose homeostasis. We used microarrays to detail the global gene expression changes in response to insulin acting through insulin receptor in osteoblasts and identified distinct genes specifically involved in bone remodeling process. 4 groups and 3 time points (0h as a control, 6h, 12h, and 24h)

2010-05-27 | E-GEOD-21710 | biostudies-arrayexpress

Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition

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Insulin receptor associates with promoters genome-wide and regulates gene expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-04-04 | GSE107336 | GEO

Insulin receptor associates with promoters genome-wide and regulates gene expression [ChIP-seq]

Project description:Insulin receptor associates with promoters genome-wide and regulates gene expression [ChIP-seq]

| PRJNA419801 | ENA

Insulin receptor associates with promoters genome-wide and regulates gene expression [RNA-seq]

Project description:Insulin receptor associates with promoters genome-wide and regulates gene expression [RNA-seq]

| PRJNA419800 | ENA

nuclear insulin receptor-associated proteins in lung cancer cells

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