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Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.

Przyborowski K, Wojewoda M, Sitek B, Zakrzewska A, Kij A, Wandzel K, Zoladz JA, Chlopicki S - PLoS ONE (2015)

Bottom Line: MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile.Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals.In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA.

View Article: PubMed Central - PubMed

Affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.

ABSTRACT
1-Methylnicotinamide (MNA), which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2). In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1), and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01). In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05). Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise.

No MeSH data available.


Related in: MedlinePlus

Diagram depicting experimental protocol.Briefly, 8-week-old db/db mice were randomly assigned into four experimental groups: sedentary, exercised mice treated with MNA (sedentary or exercised MNA) and sedentary, exercised mice not treated with MNA (sedentary or exercised control). See text for details of the experimental protocol.
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pone.0130908.g001: Diagram depicting experimental protocol.Briefly, 8-week-old db/db mice were randomly assigned into four experimental groups: sedentary, exercised mice treated with MNA (sedentary or exercised MNA) and sedentary, exercised mice not treated with MNA (sedentary or exercised control). See text for details of the experimental protocol.

Mentions: The scheme of the protocol is presented in Fig 1. 8-week-old db/db mice were randomly assigned into the following experimental groups: sedentary or exercised mice not treated with MNA (sedentary or exercised control) and sedentary or exercised mice treated with MNA (sedentary or exercised MNA). MNA was given in drinking water for 4 weeks at a dose of 100 mg·kg-1. Mice were weighed once a week in order to adjust the MNA dosage. After 4 weeks of MNA supplementation, the animals assigned into the exercised groups were subjected to endurance running tests as described below.


Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.

Przyborowski K, Wojewoda M, Sitek B, Zakrzewska A, Kij A, Wandzel K, Zoladz JA, Chlopicki S - PLoS ONE (2015)

Diagram depicting experimental protocol.Briefly, 8-week-old db/db mice were randomly assigned into four experimental groups: sedentary, exercised mice treated with MNA (sedentary or exercised MNA) and sedentary, exercised mice not treated with MNA (sedentary or exercised control). See text for details of the experimental protocol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482656&req=5

pone.0130908.g001: Diagram depicting experimental protocol.Briefly, 8-week-old db/db mice were randomly assigned into four experimental groups: sedentary, exercised mice treated with MNA (sedentary or exercised MNA) and sedentary, exercised mice not treated with MNA (sedentary or exercised control). See text for details of the experimental protocol.
Mentions: The scheme of the protocol is presented in Fig 1. 8-week-old db/db mice were randomly assigned into the following experimental groups: sedentary or exercised mice not treated with MNA (sedentary or exercised control) and sedentary or exercised mice treated with MNA (sedentary or exercised MNA). MNA was given in drinking water for 4 weeks at a dose of 100 mg·kg-1. Mice were weighed once a week in order to adjust the MNA dosage. After 4 weeks of MNA supplementation, the animals assigned into the exercised groups were subjected to endurance running tests as described below.

Bottom Line: MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile.Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals.In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA.

View Article: PubMed Central - PubMed

Affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.

ABSTRACT
1-Methylnicotinamide (MNA), which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2). In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1), and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01). In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05). Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise.

No MeSH data available.


Related in: MedlinePlus