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  • High-dose metformin (420mg/kg daily p.o.) increases insulin sensitivity but does not affect neointimal thickness in the rat carotid balloon injury model of restenosis.

High-dose metformin (420mg/kg daily p.o.) increases insulin sensitivity but does not affect neointimal thickness in the rat carotid balloon injury model of restenosis.

Metabolism: clinical and experimental (2017-02-12)
June Guo, Troy J Pereira, Prasad Dalvi, Lucy Shu Nga Yeung, Nathan Swain, Danna M Breen, Loretta Lam, Vernon W Dolinsky, Adria Giacca
RÉSUMÉ

Our laboratory has shown that insulin's effect to decrease neointimal thickness after arterial injury is greatly diminished in insulin resistant conditions. Thus, in these conditions, a better alternative to insulin could be to use an insulin sensitizing agent. Metformin, the most commonly prescribed insulin sensitizer, has a cardiovascular protective role. Therefore, the objective of this study was to investigate the potential benefit of metformin on neointimal area after arterial injury in a rat model of restenosis. Rats fed with either normal or high fat diet and treated with or without oral metformin (420mg/kg daily) underwent carotid balloon injury. Effects of metformin on clamp-determined insulin sensitivity, vessel AMPK (AMP-activated protein kinase) phosphorylation (activation marker) and neointimal area were evaluated. Metformin increased insulin sensitivity, but did not affect neointimal thickness in either the normal fat or high fat diet-fed rats. Furthermore, metformin activated AMPK in uninjured but not in injured vessels. Similarly, 10mmol/L metformin inhibited proliferation and activated AMPK in smooth muscle cells of uninjured but not injured vessels, whereas 2mmol/L metformin did not have any effect. In rats, metformin does not decrease neointimal growth after arterial injury, despite increasing whole body insulin sensitivity.

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Dulbecco′s Modified Eagle′s Medium - low glucose, With 1000 mg/L glucose, L-glutamine, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
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AICAR, ≥98% (HPLC), powder
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