SFEBES2009 Poster Presentations Diabetes, Metabolism and Cardiovascular (49 abstracts)
Heterozygous knockout of the insulin-like growth factor 1 receptor in mice leads to impaired glucose tolerance, enhanced insulin sensitivity and increased endothelial basal nitric oxide production
A Abbas , H Imrie , H Viswambharan , A Rajwani , M Kahn , R Cubbon , M Gage , S Wheatcroft , P Grant & M Kearney
University of Leeds, Leeds, UK.
Introduction: Insulin-like growth factor 1 (IGF-1), acting via similar signalling pathways to insulin, enhances glucose uptake and nitric oxide (NO) production. Observational studies suggest a role for (IGF-1) in insulin resistance and cardiovascular disease. To investigate this further we used a murine model with heterozygous knockout of the IGF-1 receptor.
Methods: Metabolic tolerance tests were performed in vivo on unanaesthetised mice, heterozygous for knockout of the IGF-1 receptor (IGF1RKO), and their wildtype littermates (WT). Ex vivo assessment of vascular function was performed using thoracic aortic rings in an organ bath.
Results: Glucose tolerance tests revealed impaired glucose handling in IGF1RKO mice compared to WT (mean AUC IGF1RKO mice=1086±26.82 (mmol/l) minutes, mean AUC WT mice=950.5±22.5 (mmol/l) minutes, n=5, P=0.005). Insulin tolerance tests revealed that IGF1RKO mice were more insulin sensitive than controls (mean AUC IGF1RKO=552.2±25.18 (mmol/l) minutes, n=10; mean AUC for WT=651.4±22.26 (mmol/l) minutes, n=11, P=0.008).
Aortic rings from IGF1RKO mice were hypocontractile to phenylepherine compared to those from WT (mean Emax IGF1RKO mice=0.60±0.05 g n=11 versus mean Emax for WT mice=0.79±0.06 g, n=10, P=0.03). Addition of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), led to a 65.40±13.40% (n=9) increase in mean Emax in IGF1RKO mice compared to 15.78±12.00% (n=9) increase in WT mice (P=0.01). In addition, IGF1RKO and WT aortic rings were equally sensitive to insulin exposure.
Conclusion: These data suggest that heterozygous knockout of IGF-1 receptor in mice leads to impaired whole body glucose handling, enhanced insulin sensitivity and increased basal NO production in the vasculature.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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