The insulin receptor substrate (IRS) proteins

Shaw, Leslie M.

doi:10.4161/cc.10.11.15824

Cited by 144 publications

(72 citation statements)

References 76 publications

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“…Such mechanisms are well established for the PI3K‐Akt pathway and evidence indicates that also the Mek‐Erk1/2 pathway is subject to analogous feedback inhibition (Carracedo et al, 2008). Among the inhibitory feedback loops, arguably the best characterized involves S6K‐dependent phosphorylation and degradation of IRS1, a large protein adaptor that recruits PI3K and components of other signaling pathways downstream of insulin or IGF receptors (Harrington et al, 2004; Haruta et al, 2000; Shaw, 2011; Takano et al, 2001). …”

Section: Mtor and Metabolismmentioning

confidence: 99%

Myelination and mTOR

Figlia

Gerber

Suter

2017

Glia

133

120

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Myelinating cells surround axons to accelerate the propagation of action potentials, to support axonal health, and to refine neural circuits. Myelination is metabolically demanding and, consistent with this notion, mTORC1—a signaling hub coordinating cell metabolism—has been implicated as a key signal for myelination. Here, we will discuss metabolic aspects of myelination, illustrate the main metabolic processes regulated by mTORC1, and review advances on the role of mTORC1 in myelination of the central nervous system and the peripheral nervous system. Recent progress has revealed a complex role of mTORC1 in myelinating cells that includes, besides positive regulation of myelin growth, additional critical functions in the stages preceding active myelination. Based on the available evidence, we will also highlight potential nonoverlapping roles between mTORC1 and its known main upstream pathways PI3K‐Akt, Mek‐Erk1/2, and AMPK in myelinating cells. Finally, we will discuss signals that are already known or hypothesized to be responsible for the regulation of mTORC1 activity in myelinating cells.

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Section: Mtor and Metabolismmentioning

confidence: 99%

Myelination and mTOR

Figlia

Gerber

Suter

2017

Glia

133

120

View full text Add to dashboard Cite

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“…Important markers that have been targeted include identification of glycated hemoglobin (HbA1c), scoring of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), blood pressure, and triglyceride levels. Evidence suggests that a longitudinal rise in either IFG or IGT has the ability to predict the development of DM, with a potential for predicting increased risk of certain cancers [145]. Because cancer and DM share so many risk factors, it seems logical that a joint prediction tool may be both feasible to develop and valuable as a diagnostic tool.…”

Section: Summary Of the Effect Of Dm Drugs On Cancer Risk And Importamentioning

confidence: 99%

Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

Onitilo

Engel

Glurich

et al. 2012

Cancer Causes Control

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An association between type 2 diabetes mellitus (DM) and cancer has long been postulated, but the biological mechanism responsible for this association has not been defined. In part one of this review, we discussed the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. Here we review the risk factors shared by cancer and DM and how DM medications play a role in altering cancer risk. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, and modulation of circulating insulin levels by DM medications appears to play an important role in altering cancer risk. Drugs that increase circulating insulin, including exogenous insulin, insulin analogs, and insulin secretagogues, are generally associated with an increased cancer risk. In contrast, drugs that regulate insulin signaling without increasing levels, especially metformin, appear to be associated with a decreased cancer risk. In addition to hyperinsulinemia, the effect of DM medications on other shared risk factors including hyperglycemia, obesity, and oxidative stress as well as demographic factors that may influence the use of certain DM drugs in different populations are described. Further elucidation of the mechanisms behind the association between DM, cancer, and the role of DM medications in modulating cancer risk may aid in the development of better prevention and treatment options for both DM and cancer. Additionally, incorporation of DM medication use into cancer prediction models may lead to the development of improved risk assessment tools for diabetic patients.

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“…[1] IGF-1R inhibitors have shown promise in the clinic in several different malignancies, including Ewing's sarcoma, non-small cell lung carcinoma, and adrenocortical carcinoma. [2-5] Both anti-IGF-1R antibodies and small molecules directed against the kinase activity of IGF-1R are being assessed in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R): Implications for Inhibition of the IGF-1R signal

et al. 2013

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It has been demonstrated that epidermal growth factor receptor (EGFR) can have kinase independent activity. EGFR kinase-independent function maintains intracellular glucose levels via sodium glucose transporter protein 1 (SGLT1) and supports cell survival. It is plausible that this phenomenon can apply to other receptor tyrosine kinases. We found that transfection of insulin-like growth factor receptor (IGF-1R) siRNA into HEK293 (human embryonic kidney) and MCF7 (metastatic breast cancer) cells results in decreased intracellular glucose levels, whereas treatment with the IGF-1R tyrosine kinase inhibitor OSI-906 did not affect intracellular glucose levels. In addition, IGF-1R interacted with SGLT1 in a manner similar to that previously reported with EGFR. The combination of IGF-1R siRNA and OSI-906 resulted in decreased viability of HEK293 and MCF7 cell lines compared to either agent alone. Collectively, these experiments suggest that IGF-1R, has kinase-independent biologic functions and provide a rationale for combining anti-IGF-1R antibodies or siRNA and IGF-1R small molecule inhibitors.

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The insulin receptor substrate (IRS) proteins

Cited by 144 publications

References 76 publications

Myelination and mTOR

Myelination and mTOR

Diabetes and cancer II: role of diabetes medications and influence of shared risk factors

A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R): Implications for Inhibition of the IGF-1R signal

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