title: Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.
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.
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Przyborowski
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Wojewoda
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zakrzewska
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kij
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wandzel
authors.affiliation: Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Krakow, Poland.
authors.forename: Jerzy Andrzej
authors.initials: JA
authors.lastname: Zoladz
authors.affiliation: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland; Department of Experimental Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011464:Epoprostenol / Q000097:blood; D008297:Male; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D005082:Physical Exertion / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D009566:Nitrates; D009573:Nitrites; D009536:Niacinamide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C024058:N(1)-methylnicotinamide