Effects of obesity on insulin: insulin-like growth factor 1 hybrid receptor expression and Akt phosphorylation in conduit and resistance arteries

Romana S. Mughal, Katherine Bridge, Irma Buza, Rita Slaaby, Jesper Worm, Gro Klitgaard-Povlsen, Henning Hvid, Marianne Schiødt, Richard Cubbon, Nadira Yuldasheva, Anna Skromna, Natallia Makava, Grith Skytte-Olsen, Mark T. Kearney

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish
Pages160-170
Number of pages11
JournalDiabetes and Vascular Disease Research
Volume16
Issue number2
Early online date8 Oct 2018
DOIs
Publication statusPublished - 1 Mar 2019
Externally publishedYes

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Somatomedins
High Fat Diet
Arteries
Obesity
Phosphorylation
Insulin
Somatomedin Receptors
Insulin Receptor
Vasodilation
Blood Vessels
Aorta
Fat-Restricted Diet
Vascular Diseases
Cues
Diet

Cite this

Mughal, Romana S. ; Bridge, Katherine ; Buza, Irma ; Slaaby, Rita ; Worm, Jesper ; Klitgaard-Povlsen, Gro ; Hvid, Henning ; Schiødt, Marianne ; Cubbon, Richard ; Yuldasheva, Nadira ; Skromna, Anna ; Makava, Natallia ; Skytte-Olsen, Grith ; Kearney, Mark T. / Effects of obesity on insulin : insulin-like growth factor 1 hybrid receptor expression and Akt phosphorylation in conduit and resistance arteries. In: Diabetes and Vascular Disease Research. 2019 ; Vol. 16, No. 2. pp. 160-170.
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Mughal, RS, Bridge, K, Buza, I, Slaaby, R, Worm, J, Klitgaard-Povlsen, G, Hvid, H, Schiødt, M, Cubbon, R, Yuldasheva, N, Skromna, A, Makava, N, Skytte-Olsen, G & Kearney, MT 2019, 'Effects of obesity on insulin: insulin-like growth factor 1 hybrid receptor expression and Akt phosphorylation in conduit and resistance arteries', Diabetes and Vascular Disease Research, vol. 16, no. 2, pp. 160-170. https://doi.org/10.1177/1479164118802550

Effects of obesity on insulin : insulin-like growth factor 1 hybrid receptor expression and Akt phosphorylation in conduit and resistance arteries. / Mughal, Romana S.; Bridge, Katherine; Buza, Irma; Slaaby, Rita; Worm, Jesper; Klitgaard-Povlsen, Gro; Hvid, Henning; Schiødt, Marianne; Cubbon, Richard; Yuldasheva, Nadira; Skromna, Anna; Makava, Natallia; Skytte-Olsen, Grith; Kearney, Mark T.

In: Diabetes and Vascular Disease Research, Vol. 16, No. 2, 01.03.2019, p. 160-170.

Research output: Contribution to journalArticle

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AU - Bridge, Katherine

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AU - Slaaby, Rita

AU - Worm, Jesper

AU - Klitgaard-Povlsen, Gro

AU - Hvid, Henning

AU - Schiødt, Marianne

AU - Cubbon, Richard

AU - Yuldasheva, Nadira

AU - Skromna, Anna

AU - Makava, Natallia

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AU - Kearney, Mark T.

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