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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


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).


PubMed PMC3142083 Online version:10.2337/db11-0197


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