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Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart.

Sukhodub A, Sudhir R, Du Q, Jovanović S, Reyes S, Jovanović A - J. Cell. Mol. Med. (2011)

Bottom Line: We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A.The experiments focused on action membrane potential and intracellular Ca(2+) concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal K(ATP) channels and steady Ca(2+) levels in cardiomyocytes in response to β-adrenergic stimulation.The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.

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Physical endurance in Kir6.2 knockout (Kir6.2 KO) mice on control and nicotinamide-rich diet. Bar graphs showing energy expenditure (A) and time spent (B) on treadmill of Kir6.2 KO mice on control and nicotinamide-rich diet. Each bar represents mean ± S.E. of the mean (n = 6–7).
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fig07: Physical endurance in Kir6.2 knockout (Kir6.2 KO) mice on control and nicotinamide-rich diet. Bar graphs showing energy expenditure (A) and time spent (B) on treadmill of Kir6.2 KO mice on control and nicotinamide-rich diet. Each bar represents mean ± S.E. of the mean (n = 6–7).

Mentions: In addition to up-regulating SUR2A expression, nicotinamide-rich diet could have other cardiac effects [31] and these might have effect on physical endurance. It was, therefore, possible that some mechanisms additional to up-regulation of SUR2A and sarcolemmal KATP channels could mediate the effect of nicotinamide-rich diet on physical endurance. To confirm or exclude this possibility, we have used Kir6.2 knockout mice. These mice have disrupted Kir6.2 gene and are lacking KATP channels in the heart and any intervention that alter the number/activity of KATP channels is ineffective in these mice. Consequently, if nicotinamide-rich diet improves physical endurance solely due to up-regulation of SUR2A and sarcolemmal KATP channels, this intervention would have no effect on physical endurance of Kir6.2 knockout mice. In contrast, if there is non-KATP channels mechanism involved, nicotinamide-rich diet would improve physical endurance in Kir6.2 knockout mice. Here, we have found that the tolerated workload was not different between mice on control and nicotinamide-rich diet; tolerated workload was 28.4 ± 1.4 J in mice on control and 28.0 ± 1.8 J in mice on nicotinamide-rich diet (n = 6–7, P = 0.95; Fig. 7). Time spent on treadmill was also not significantly different (Fig. 7).


Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart.

Sukhodub A, Sudhir R, Du Q, Jovanović S, Reyes S, Jovanović A - J. Cell. Mol. Med. (2011)

Physical endurance in Kir6.2 knockout (Kir6.2 KO) mice on control and nicotinamide-rich diet. Bar graphs showing energy expenditure (A) and time spent (B) on treadmill of Kir6.2 KO mice on control and nicotinamide-rich diet. Each bar represents mean ± S.E. of the mean (n = 6–7).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373361&req=5

fig07: Physical endurance in Kir6.2 knockout (Kir6.2 KO) mice on control and nicotinamide-rich diet. Bar graphs showing energy expenditure (A) and time spent (B) on treadmill of Kir6.2 KO mice on control and nicotinamide-rich diet. Each bar represents mean ± S.E. of the mean (n = 6–7).
Mentions: In addition to up-regulating SUR2A expression, nicotinamide-rich diet could have other cardiac effects [31] and these might have effect on physical endurance. It was, therefore, possible that some mechanisms additional to up-regulation of SUR2A and sarcolemmal KATP channels could mediate the effect of nicotinamide-rich diet on physical endurance. To confirm or exclude this possibility, we have used Kir6.2 knockout mice. These mice have disrupted Kir6.2 gene and are lacking KATP channels in the heart and any intervention that alter the number/activity of KATP channels is ineffective in these mice. Consequently, if nicotinamide-rich diet improves physical endurance solely due to up-regulation of SUR2A and sarcolemmal KATP channels, this intervention would have no effect on physical endurance of Kir6.2 knockout mice. In contrast, if there is non-KATP channels mechanism involved, nicotinamide-rich diet would improve physical endurance in Kir6.2 knockout mice. Here, we have found that the tolerated workload was not different between mice on control and nicotinamide-rich diet; tolerated workload was 28.4 ± 1.4 J in mice on control and 28.0 ± 1.8 J in mice on nicotinamide-rich diet (n = 6–7, P = 0.95; Fig. 7). Time spent on treadmill was also not significantly different (Fig. 7).

Bottom Line: We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A.The experiments focused on action membrane potential and intracellular Ca(2+) concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal K(ATP) channels and steady Ca(2+) levels in cardiomyocytes in response to β-adrenergic stimulation.The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, Centre for Cardiovascular and Lung Biology, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.

Show MeSH