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Effects of 1-methylnicotinamide (MNA) on exercise capacity and endothelial response in diabetic mice
1-methylnicotinamide
6-oxoprostaglandin F1 alpha
nitrate
nitrite
animal experiment
article
cardiovascular risk
controlled study
diabetes mellitus
drug blood level
endurance training
exercise intensity
heart protection
insulin sensitivity
leukocytosis
male
mouse
nonhuman
physical capacity
running
treatment response
vascular endothelium
animalia
mus
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.
cris.lastimport.scopus | 2024-04-07T17:49:08Z | |
cris.lastimport.wos | 2024-04-10T00:29:04Z | |
dc.abstract.en | 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 (PGI<inf>2</inf>). 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 PGI<inf>2</inf>-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 HbA<inf>1c</inf> 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-PGF<inf>1α</inf> (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. | pl |
dc.affiliation | Pion Rektora : Jagiellońskie Centrum Rozwoju Leków | pl |
dc.affiliation | Wydział Lekarski : Zakład Farmakologii | pl |
dc.cm.id | 73242 | |
dc.contributor.author | Przyborowski, Kamil - 243634 | pl |
dc.contributor.author | Wojewoda, Marta - 214381 | pl |
dc.contributor.author | Sitek, Barbara - 200898 | pl |
dc.contributor.author | Zakrzewska, Agnieszka - 198214 | pl |
dc.contributor.author | Kij, Agnieszka - 215016 | pl |
dc.contributor.author | Wandzel, Krystyna - 200692 | pl |
dc.contributor.author | Zoladz, Jerzy Andrzej | pl |
dc.contributor.author | Chłopicki, Stefan - 128995 | pl |
dc.date.accessioned | 2016-08-22T08:25:20Z | |
dc.date.available | 2016-08-22T08:25:20Z | |
dc.date.issued | 2015 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.number | 6 | pl |
dc.description.physical | [1-15] | pl |
dc.description.points | 40 | pl |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 10 | pl |
dc.identifier.articleid | e0130908 | pl |
dc.identifier.doi | 10.1371/journal.pone.0130908 | pl |
dc.identifier.eissn | 1932-6203 | pl |
dc.identifier.project | ROD UJ / P | pl |
dc.identifier.uri | http://ruj.uj.edu.pl/xmlui/handle/item/29753 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | * |
dc.rights.licence | CC-BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | * |
dc.share.type | otwarte czasopismo | |
dc.subject.en | 1-methylnicotinamide | pl |
dc.subject.en | 6-oxoprostaglandin F1 alpha | pl |
dc.subject.en | nitrate | pl |
dc.subject.en | nitrite | pl |
dc.subject.en | animal experiment | pl |
dc.subject.en | article | pl |
dc.subject.en | cardiovascular risk | pl |
dc.subject.en | controlled study | pl |
dc.subject.en | diabetes mellitus | pl |
dc.subject.en | drug blood level | pl |
dc.subject.en | endurance training | pl |
dc.subject.en | exercise intensity | pl |
dc.subject.en | heart protection | pl |
dc.subject.en | insulin sensitivity | pl |
dc.subject.en | leukocytosis | pl |
dc.subject.en | male | pl |
dc.subject.en | mouse | pl |
dc.subject.en | nonhuman | pl |
dc.subject.en | physical capacity | pl |
dc.subject.en | running | pl |
dc.subject.en | treatment response | pl |
dc.subject.en | vascular endothelium | pl |
dc.subject.en | animalia | pl |
dc.subject.en | mus | pl |
dc.subtype | Article | pl |
dc.title | Effects of 1-methylnicotinamide (MNA) on exercise capacity and endothelial response in diabetic mice | pl |
dc.title.journal | PLoS ONE | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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