Insulin Stimulates Production of Nitric Oxide via ERK in Osteoblast Cells

Kim, Sungjin; Chun, Jong-Yoon; Kim, Mi-Sun

doi:10.1006/bbrc.2000.3862

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…For example, Begum and Ragolia [37] reported that 100 nM insulin upregulated iNOS protein levels by nearly three-fold in rat vascular smooth muscle cells. Kim et al [38] reported similar findings for rat osteoblast-like cells. Specifically, 10 nM insulin induced NO synthesis 1.3-fold and 100 nM insulin induced NO synthesis two-fold relative to controls [38].…”

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Csupporting

confidence: 54%

“…Kim et al [38] reported similar findings for rat osteoblast-like cells. Specifically, 10 nM insulin induced NO synthesis 1.3-fold and 100 nM insulin induced NO synthesis two-fold relative to controls [38]. Insulin induction of NO synthesis was inhibited by the MEK inhibitor PD98059 and induced by overexpression of Erk, indicating that insulin induced NO synthesis via activation of a MEK/Erk-dependent pathway [38].…”

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Csupporting

confidence: 54%

“…Specifically, 10 nM insulin induced NO synthesis 1.3-fold and 100 nM insulin induced NO synthesis two-fold relative to controls [38]. Insulin induction of NO synthesis was inhibited by the MEK inhibitor PD98059 and induced by overexpression of Erk, indicating that insulin induced NO synthesis via activation of a MEK/Erk-dependent pathway [38]. In contrast to insulin, 100 nM IGF-1 increased NO synthesis by only 57% relative to controls, indicating that iNOS activity in osteoblast-like cells is significantly more sensitive to regulation by insulin than by IGF-1 [38].…”

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Cmentioning

confidence: 93%

“…Insulin induction of NO synthesis was inhibited by the MEK inhibitor PD98059 and induced by overexpression of Erk, indicating that insulin induced NO synthesis via activation of a MEK/Erk-dependent pathway [38]. In contrast to insulin, 100 nM IGF-1 increased NO synthesis by only 57% relative to controls, indicating that iNOS activity in osteoblast-like cells is significantly more sensitive to regulation by insulin than by IGF-1 [38]. In other studies, treatment of human endothelial cells with a concentration of insulin closer to physiological levels (1nM) induced NO synthesis via insulin receptor activation and activation of a downstream pertussis-sensitive GTP-binding protein and Erk 1/2-dependent signaling [39].…”

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Cmentioning

confidence: 99%

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The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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As revealed over the past twenty years, the insulin signaling cascade plays a central role in regulating immune and oxidative stress responses that affect the life spans of mammals and two model invertebrates, the nematode Caenorhabitis elegans and the fruit fly Drosophila melanogaster. In mosquitoes, insulin signaling regulates key steps in egg maturation and immunity and likely affects aging, although the latter has yet to be examined in detail. Reproduction, immunity and aging critically influence the capacity of mosquitoes to effectively transmit malaria parasites. Current work has demonstrated that molecules from the invading parasite and the blood meal elicit functional responses in female mosquitoes that are regulated through the insulin signaling pathway or by crosstalk with interacting pathways. Defining the details of these regulatory interactions presents significant challenges for future research, but will increase our understanding of mosquito/malaria parasite transmission and of the conservation of insulin signaling as a key regulatory nexus in animal biology. Keywordsinsulin; Anopheles; Plasmodium; mosquito; malaria; aging; oxidative stress; innate immunity; nitric oxide; transforming growth factor; β In all well-studied metazoans, metabolism, growth, and longevity are coordinately regulated via a nexus that involves signaling cascades activated by insulin and insulin-like growth factors (IGF). Although these pathways differ in downstream physiological effects and some of their signaling proteins, the proteins themselves and their scaffolding interactions are largely conserved among model organisms ( Fig. 1), particularly in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse Mus musculus. This review will examine our current understanding of how the insulin and IGF signaling cascades (ISC) regulate immunity in these diverse model organisms. In addition, we will explore how recent Correspondence to: Shirley Luckhart. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Key targets of daf-16 regulation include genes for mitochondrial manganese superoxide dismutase (MnSOD) and glutathione S-transferase, which are closely linked to aging in C. elegans and other organisms, and genes for numerous C-type lectins, which play critical roles in cell adhesion and pathogen recognition [5]. Downregulation of these gene targets in daf-16 mutants would be predicted to enhance oxidative stress, which has been linked directly to aging in C. elegans [6,7], and decrease pathogen recognition [8]. Conversely, rescue of downregulated MnSOD...

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Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Csupporting

confidence: 54%

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Csupporting

confidence: 54%

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Cmentioning

confidence: 93%

Section: The Isc and Nitric Oxide In Mammals: Positive Feedback And Cmentioning

confidence: 99%

See 2 more Smart Citations

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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“…14,15 Second, the UMR cell line was originally derived from an induced paraosteal osteosarcoma of the Sprague-Dawley rat, 16 and the bone tissues in this breed of rat have been proven to respond anabolically to both PTH and PEMF. 4,17 Finally, our intent was to use the UMR cell line to complement other ongoing, parallel studies utilizing the effects of PEMF treatment in another osteoblastic cell line, MC3T3-E1.…”

Section: Cell Culturing Proceduresmentioning

confidence: 99%

Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: Comparison to parathyroid hormone and insulin

Schnoke

Midura

2007

Journal Orthopaedic Research

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Pulsed electromagnetic field (PEMF) devices are approved for the healing of bone nonunions, but there is a lack of understanding as to their mechanism of action at the cell and molecular level. Intermittent parathyroid hormone (PTH) therapy is currently utilized for treatment of osteoporosis, and is also being investigated for the purpose of augmenting fracture healing. Insulin and IGF-1 are also thought to play important anabolic roles in osteogenesis. In this report, signaling pathways activated by acute PTH or insulin treatments were compared to those activated by PEMF treatment in osteoblast-like cells. Some signaling molecules like the extracellular response kinases 1/2 (Erk1/2) and the cAMP response element binding protein (CREB) were activated by insulin and PTH, respectively, but not by PEMF treatment. Other signaling molecules like the insulin receptor substrate-1 (IRS-1), the S6 ribosomal subunit kinase, and the endothelial nitric oxide synthase (eNOS) were phosphorylated by PTH, insulin, and PEMF to the same relative extent and within the same time frame. IRS-1, eNOS, and S6 have been implicated in bone anabolism, and our results suggest that the anabolic effects of PEMF may be mediated, in part, through the activation of these proteins. ß

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Insulin stimulates gene expression of ferritin light chain in osteoblast cells

Han

Saminathan

Kim

2010

J of Cellular Biochemistry

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We explored to identify differentially expressed gene(s) by insulin in osteoblast-like UMR-106 cells by employing annealing control primer (ACP)-based GeneFishing PCR. UMR-106 cells were treated with insulin and total RNA was isolated. The GeneFishing differential display (DD) PCR was carried out and the profiles of expressed genes were compared between control and insulin treated group, and followed by cloning, sequencing and screened by a BLAST search. It has been found that expression of a PCR product was significantly increased by insulin: It was identified as ferritin light chain. It was further confirmed by reverse transcriptase-PCR (RT-PCR) analysis that insulin significantly stimulates the mRNA expression of ferritin light chain. In a Western blot analysis, insulin also increased the protein expression of ferritin light chain. When ERK inhibitor or Casein Kinase II inhibitor (DRB) was pretreated, the stimulation of ferritin light chain expression by insulin was significantly inhibited, suggesting that ERK I/II or Casein Kinase II may play a role in the insulin stimulated increase of ferritin light chain. These results suggest that insulin may play an important role in Fe metabolism in osteoblast cells.

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Insulin Stimulates Production of Nitric Oxide via ERK in Osteoblast Cells

Cited by 13 publications

References 44 publications

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: Comparison to parathyroid hormone and insulin

Insulin stimulates gene expression of ferritin light chain in osteoblast cells

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