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PMID:21677284

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Citation

Abbas, A, Imrie, H, Viswambharan, H, Sukumar, P, Rajwani, A, Cubbon, RM, Gage, M, Smith, J, Galloway, S, Yuldeshava, N, Kahn, M, Xuan, S, Grant, PJ, Channon, KM, Beech, DJ, Wheatcroft, SB and Kearney, MT (2011) The insulin-like growth factor-1 receptor is a negative regulator of nitric oxide bioavailability and insulin sensitivity in the endothelium. Diabetes 60:2169-78

Abstract

In mice, haploinsufficiency of the IGF-1 receptor (IGF-1R(+/-)), at a whole-body level, increases resistance to inflammation and oxidative stress, but the underlying mechanisms are unclear. We hypothesized that by forming insulin-resistant heterodimers composed of one IGF-1Rαβ and one insulin receptor (IR), IRαβ complex in endothelial cells (ECs), IGF-1R reduces free IR, which reduces EC insulin sensitivity and generation of the antioxidant/anti-inflammatory signaling radical nitric oxide (NO).

Links

PubMed PMC3142083 Online version:10.2337/db11-0197

Keywords

Animals; Aorta/drug effects; Biological Availability; Down-Regulation; Endothelial Cells/metabolism; Glucose/metabolism; Glucose Intolerance/genetics; Humans; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Nitric Oxide/metabolism; Nitric Oxide Synthase Type III/metabolism; Phenylephrine/pharmacology; Receptor, IGF Type 1/deficiency; Receptor, IGF Type 1/genetics; Receptor, IGF Type 1/physiology; Receptor, Insulin/genetics; Receptor, Insulin/physiology; Signal Transduction; Umbilical Veins/cytology; Vasoconstriction/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IGF1

enables

GO:0005158: insulin receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:IGF1

acts_upstream_of_or_within

GO:0050732: negative regulation of peptidyl-tyrosine phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2386329

P

Seeded From UniProt

complete

MOUSE:IGF1

acts_upstream_of_or_within

GO:0045428: regulation of nitric oxide biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2386329
MGI:MGI:2389580

P

Seeded From UniProt

complete

MOUSE:IGF1

acts_upstream_of_or_within

GO:0071333: cellular response to glucose stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IGF1

acts_upstream_of_or_within

GO:1990314: cellular response to insulin-like growth factor stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2386329

P

Seeded From UniProt

complete

MOUSE:IGF1R

acts_upstream_of_or_within

GO:0071333: cellular response to glucose stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2386329

P

Seeded From UniProt

complete

MOUSE:IGF1R

acts_upstream_of_or_within

GO:0032869: cellular response to insulin stimulus

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2386329

P

Seeded From UniProt

complete

Notes

See also

References

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