Endocrine Abstracts

Introduction: Accumulating evidence suggests a role for IGF1 in insulin resistance and cardiovascular disease. IGF1 enhances glucose uptake and nitric oxide (NO) production, via similar mechanisms to insulin. Previously we have reported a mouse model with global heterozygous knockout of the IGF1 receptor (IGF1RKO) that has enhanced insulin sensitivity and increased nitric oxide (NO) production in the vasculature.Methods: To investigate this further we us...

Endothelial dysfunction is a key step in the initiation of atherosclerosis, resulting from a decrease in bioavailability of nitric oxide (NO). IGF-1 may play a part in regulation of NO production via the PI3-kinase/Akt/eNOS pathway. We have investigated whether disturbances of this pathway occur in dietary-induced obesity.Obesity was induced in mice fed a high fat diet for 20 weeks (n=12), compared to chow fed controls, with an age-related increas...

Aldosterone is a key cardiovascular hormone: 15% of hypertensives have altered aldosterone regulation, defined by a raised ratio of aldosterone to renin. However, the causes of aldosterone excess are not understood. Polymorphic variation in the gene encoding aldosterone synthase (CYP11B2) is associated with hypertension, but the most robust phenotype is a relative reduction in efficiency of 11ß-hydroxylation (conversion of deoxycortisol to cortisol), which reflects functi...

Type 2 diabetes is preceded by insulin resistance, followed by increased endothelial cell production of superoxide and reduction in bioavailability of the vasoprotective signalling molecule, nitric oxide (NO). We demonstrated in preclinical models that type 2 diabetes also causes resistance to insulin-like growth factor-1 (IGF-1) mediated glucose lowering and endothelial NO release. This study aimed to examine the effect of the endothelial cell-specific combination of insulin ...