%0 Journal Article %T Effects of obesity on insulin: insulin %A Anna Skromna %A Grith Skytte-Olsen %A Gro Klitgaard-Povlsen %A Henning Hvid %A Irma Buza %A Jesper Worm %A Katherine Bridge %A Marianne Schi£¿dt %A Mark T Kearney %A Nadira Yuldasheva %A Natallia Makava %A Richard Cubbon %A Rita Slaaby %A Romana S Mughal %J Diabetes and Vascular Disease Research %@ 1752-8984 %D 2019 %R 10.1177/1479164118802550 %X Insulin and insulin-like growth factor-1 stimulate specific responses in arteries, which may be disrupted by diet-induced obesity. We examined (1) temporal effects of high-fat diet compared to low-fat diet in mice on insulin receptor, insulin-like growth factor-1 receptor, insulin receptor/insulin-like growth factor-1 receptor hybrid receptor expression and insulin/insulin-like growth factor-1-mediated Akt phosphorylation in aorta; and (2) effects of high-fat diet on insulin and insulin-like growth factor-1-mediated Akt phosphorylation and vascular tone in resistance arteries. Medium-term high-fat diet (5£¿weeks) decreased insulin-like growth factor-1 receptor expression and increased hybrid expression (~30%) only. After long-term (16£¿weeks) high-fat diet, insulin receptor expression was reduced by ~30%, insulin-like growth factor-1 receptor expression decreased a further ~40% and hybrid expression increased a further ~60%. Independent correlates of hybrid receptor expression were high-fat diet, duration of high-fat diet and plasma insulin-like growth factor-1 (all p£¿<£¿0.05). In aorta, insulin was a more potent activator of Akt than insulin-like growth factor-1, whereas in resistance arteries, insulin-like growth factor-1 was more potent than insulin. High-fat diet blunted insulin-mediated vasorelaxation (p£¿<£¿0.01) but had no effect on insulin-like growth factor-1-mediated vasorelaxation in resistance arteries. Our findings support the possibility that hybrid receptor level is influenced by nutritional and metabolic cues. Moreover, vessel-dependent effects of insulin and insulin-like growth factor-1 on vascular tone and Akt activation may have implications in treating obesity-related vascular disease %K Obesity %K IGF-1 receptors %K hybrid receptors %U https://journals.sagepub.com/doi/full/10.1177/1479164118802550