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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

Post-exercise plasma concentration of 6-keto-PGF1α (A) nitrite (B) and nitrate (C) in untreated and MNA-treated db/db mice.Delta (Δ) denotes the difference between the mean concentration of a given metabolite determined at rest in the sedentary group and in the exercised group of mice after completing the fatiguing run. Data are presented as the mean ±SEM. Statistical analysis was performed using the Mann-Whitney test or unpaired t-test depending on the results of the normality test. *P<0.05, **P<0.01, ***P<0.001 vs. corresponding sedentary group (n = 6–12).
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pone.0130908.g007: Post-exercise plasma concentration of 6-keto-PGF1α (A) nitrite (B) and nitrate (C) in untreated and MNA-treated db/db mice.Delta (Δ) denotes the difference between the mean concentration of a given metabolite determined at rest in the sedentary group and in the exercised group of mice after completing the fatiguing run. Data are presented as the mean ±SEM. Statistical analysis was performed using the Mann-Whitney test or unpaired t-test depending on the results of the normality test. *P<0.05, **P<0.01, ***P<0.001 vs. corresponding sedentary group (n = 6–12).

Mentions: Endurance exercise induced a significant increase in 6-keto-PGF1α plasma concentration in both untreated (4862±684.9 vs. 6828±419 pg·ml-1, P<0.05, n = 7–10) and MNA-treated db/db mice (3263±860.7 vs. 9204±1716 vs. pg·ml-1, P<0.05, n = 7–12) (Fig 7A). The post-exercise 6-keto-PGF1α plasma concentration in MNA-treated db/db mice was not significantly different from untreated db/db mice, however, the post-exercise increase in 6-keto-PGF1α (Δ6-keto-PGF1α) plasma concentration was higher in MNA-treated animals (Δ6-keto-PGF1α = 5941 in MNA group vs. 1966 pg·ml-1 in control group, Fig 7A). There were no significant differences in nitrite and nitrate plasma concentrations between sedentary untreated and sedentary MNA-treated db/db mice (Fig 7B and 7C), although in untreated and MNA-treated mice, the post-exercise plasma concentrations of nitrate were significantly lower (Fig 7C). The post-exercise fall in plasma nitrate concentration was similar for both untreated and MNA-treated groups (for untreated group ΔNO3- = 49.48 and for MNA-treated group Δ = 51.85, Fig 7C). The post-exercise concentration of nitrite only tended to fall in the untreated and MNA-treated groups, and there was no difference between groups (Fig 7B).


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)

Post-exercise plasma concentration of 6-keto-PGF1α (A) nitrite (B) and nitrate (C) in untreated and MNA-treated db/db mice.Delta (Δ) denotes the difference between the mean concentration of a given metabolite determined at rest in the sedentary group and in the exercised group of mice after completing the fatiguing run. Data are presented as the mean ±SEM. Statistical analysis was performed using the Mann-Whitney test or unpaired t-test depending on the results of the normality test. *P<0.05, **P<0.01, ***P<0.001 vs. corresponding sedentary group (n = 6–12).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130908.g007: Post-exercise plasma concentration of 6-keto-PGF1α (A) nitrite (B) and nitrate (C) in untreated and MNA-treated db/db mice.Delta (Δ) denotes the difference between the mean concentration of a given metabolite determined at rest in the sedentary group and in the exercised group of mice after completing the fatiguing run. Data are presented as the mean ±SEM. Statistical analysis was performed using the Mann-Whitney test or unpaired t-test depending on the results of the normality test. *P<0.05, **P<0.01, ***P<0.001 vs. corresponding sedentary group (n = 6–12).
Mentions: Endurance exercise induced a significant increase in 6-keto-PGF1α plasma concentration in both untreated (4862±684.9 vs. 6828±419 pg·ml-1, P<0.05, n = 7–10) and MNA-treated db/db mice (3263±860.7 vs. 9204±1716 vs. pg·ml-1, P<0.05, n = 7–12) (Fig 7A). The post-exercise 6-keto-PGF1α plasma concentration in MNA-treated db/db mice was not significantly different from untreated db/db mice, however, the post-exercise increase in 6-keto-PGF1α (Δ6-keto-PGF1α) plasma concentration was higher in MNA-treated animals (Δ6-keto-PGF1α = 5941 in MNA group vs. 1966 pg·ml-1 in control group, Fig 7A). There were no significant differences in nitrite and nitrate plasma concentrations between sedentary untreated and sedentary MNA-treated db/db mice (Fig 7B and 7C), although in untreated and MNA-treated mice, the post-exercise plasma concentrations of nitrate were significantly lower (Fig 7C). The post-exercise fall in plasma nitrate concentration was similar for both untreated and MNA-treated groups (for untreated group ΔNO3- = 49.48 and for MNA-treated group Δ = 51.85, Fig 7C). The post-exercise concentration of nitrite only tended to fall in the untreated and MNA-treated groups, and there was no difference between groups (Fig 7B).

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