| Autor: |
Mughal RS; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Bridge K; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Buza I; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Slaaby R; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Worm J; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Klitgaard-Povlsen G; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Hvid H; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Schiødt M; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Cubbon R; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Yuldasheva N; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Skromna A; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Makava N; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK., Skytte-Olsen G; 2 Global Research, Novo Nordisk A/S, Malov, Denmark., Kearney MT; 1 Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), School of Medicine, University of Leeds, Leeds, UK. |
| Abstrakt: |
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. |
