Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice

Page, Melissa M.; Schuster, Eugene; Mudaliar, Manikhandan; Herzyk, Pawel; Withers, Dominic J.; Selman, Colin

doi:10.18632/aging.101446

Cited by 9 publications

(13 citation statements)

References 85 publications

(103 reference statements)

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“…As an important mediator of insulin binding to its receptors and exerting biological effects, IRS1 plays an important role in the control of blood glucose homeostasis . A recent study suggests that the cause of insulin deficiency in obese patients may be due to a weakened IRS1 signal .…”

Section: Discussionmentioning

confidence: 99%

“…As an important mediator of insulin binding to its receptors and exerting biological effects, IRS1 plays an important role in the control of blood glucose homeostasis. 19 A recent study suggests that the cause of insulin deficiency in obese patients may be due to a weakened IRS1 signal. 20 A study of African-Americans found that IRS1 mutations and endocrine disorders caused by obesity synergistically reduce insulin sensitivity, suggesting that IRS1 variability and obesity together become an important predictor of insulin resistance.…”

Section: Gene Name Patient Num Patientmentioning

confidence: 99%

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Combined analysis of whole‐exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity

Zhang²,

Liu

et al. 2020

J Cell Mol Med

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This study sought to find more exon mutation sites and lncRNA candidates associated with type 2 diabetes mellitus (T2DM) patients with obesity (O‐T2DM). We used O‐T2DM patients and healthy individuals to detect mutations in their peripheral blood by whole‐exon sequencing. And changes in lncRNA expression caused by mutation sites were studied at the RNA level. Then, we performed GO analysis and KEGG pathway analysis. We found a total of 277 377 mutation sites between O‐T2DM and healthy individuals. Then, we performed a DNA‐RNA joint analysis. Based on the screening of harmful sites, 30 mutant genes shared in O‐T2DM patients were screened. At the RNA level, mutations of 106 differentially expressed genes were displayed. Finally, a consensus mutation site and differential expression consensus gene screening were performed. In the current study, the results revealed significant differences in exon sites in peripheral blood between O‐T2DM and healthy individuals, which may play an important role in the pathogenesis of O‐T2DM by affecting the expression of the corresponding lncRNA. This study provides clues to the molecular mechanisms of metabolic disorders in O‐T2DM patients at the DNA and RNA levels, as well as biomarkers of the risk of these disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Gene Name Patient Num Patientmentioning

confidence: 99%

Combined analysis of whole‐exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity

Zhang²,

Liu

et al. 2020

J Cell Mol Med

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“…Interventions to disrupt the GH/IGF-1 (somatotropic) axis have been shown to have pro-longevity effects in mice. For example, mice with deletion of insulin receptor substrate 1 (IRS1) are long-lived with delay age-related processes [49]. Knockout of the mouse growth hormone receptor/binding protein (GHR/BP) gene also results in an extended lifespan [44,50,51].…”

Section: Signaling Network Of Foxo In Dr: Insulin/igf-1 Signaling Pamentioning

confidence: 99%

Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction

Shao

Yan

Feng

et al. 2019

Cells

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Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span.

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“…measured liver, muscle, brain and WAT transcriptomes in middle age (15 months old) female Irs1 − / − mice using an RNA-sequencing approach. They identified 124 DEGs (FDR < 0.1) in the liver, 185 DEGs in muscle, 111 DEGs in brain, and 344 DEGs in WAT (89). There was no common DEG across the four different tissues.…”

Section: Tissue-specific Effects Of Gh-iis Axismentioning

confidence: 99%

Growth signaling and longevity in mouse models

Kim

Lee

2019

BMB Rep.

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Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

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Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice

Cited by 9 publications

References 85 publications

Combined analysis of whole‐exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity

Combined analysis of whole‐exon sequencing and lncRNA sequencing in type 2 diabetes mellitus patients with obesity

Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction

Growth signaling and longevity in mouse models

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